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Kazmi SZ, Jung HS, Han Y, Yun WG, Cho YJ, Lee M, Kwon W, Castillo CFD, Del Chiaro M, Marchegiani G, Goh BKP, Hijioka S, Majumder S, Nakai Y, Shin A, Jang JY. Systematic review on surveillance for non-resected branch-duct intraductal papillary mucinous neoplasms of the pancreas. Pancreatology 2024; 24:463-488. [PMID: 38480047 DOI: 10.1016/j.pan.2024.02.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2023] [Revised: 01/08/2024] [Accepted: 02/24/2024] [Indexed: 04/19/2024]
Abstract
BACKGROUND The management of branch-duct type intraductal papillary mucinous neoplasms (BD-IPMN) varies in existing guidelines. This study investigated the optimal surveillance protocol and safe discontinuation of surveillance considering natural history in non-resected IPMN, by systematically reviewing the published literature. METHODS This review was guided by PRISMA. Research questions were framed in PICO format "CQ1-1: Is size criteria helpful to determine surveillance period? CQ1-2: How often should surveillance be carried out? CQ1-3: When should surveillance be discontinued? CQ1-4: Is nomogram predicting malignancy useful during surveillance?". PubMed was searched from January-April 2022. RESULTS The search generated 2373 citations. After screening, 83 articles were included. Among them, 33 studies were identified for CQ1-1, 19 for CQ1-2, 26 for CQ1-3 and 12 for CQ1-4. Cysts <1.5 or 2 cm without worrisome features (WF) were described as more indolent, and most studies advised an initial period of surveillance. The median growth rate of cysts <2 cm ranged from 0.23 to 0.6 mm/year. Patients with cysts <2 cm showing no morphological changes and no WF after 5-years of surveillance have minimal malignancy risk of 0-2%. Two nomograms created with over 1000 patients had AUCs of around 0.8 and appear to be feasible in a real-world practice. CONCLUSIONS For patients with suspected BD-IPMN <2 cm and no other WF, less frequent surveillance is recommended. Surveillance may be discontinued for cysts that remain stable during 5-year surveillance, with consideration of patient condition and life expectancy. With this updated surveillance strategy, patients with non-worrisome BD-IPMN should expect more streamlined management and decreased healthcare utilization.
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Affiliation(s)
- Sayada Zartasha Kazmi
- Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, South Korea
| | - Hye-Sol Jung
- 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
| | - Won-Gun Yun
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Young Jae Cho
- 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
| | - Wooil Kwon
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | | | - Marco Del Chiaro
- Division of Surgical Oncology, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Giovanni Marchegiani
- Department of Surgery, Oncology and Gastroenterology (DiSCOG), Padova University Hospital, Padova, Italy
| | - Brian K P Goh
- Department of Hepatopancreatobiliary and Transplantation Surgery, Singapore General Hospital & National Cancer Centre Singapore, Singapore
| | - Susumu Hijioka
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Chuo-ku, Japan
| | - Shounak Majumder
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Yousuke Nakai
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Aesun Shin
- Department of Preventive Medicine and Cancer Research Institute, Seoul National University, Seoul, South Korea.
| | - Jin-Young Jang
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea.
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Na JE, Park JK, Lee JK, Park JK, Lee KH, Lee KT. Comparison of Clinical and Imaginal Features According to the Pathological Grades of Dysplasia in Branch-Duct Intraductal Papillary Mucinous Neoplasm (BD-IPMN) for Personalized Medicine. J Pers Med 2023; 13:149. [PMID: 36675810 PMCID: PMC9863534 DOI: 10.3390/jpm13010149] [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: 11/30/2022] [Revised: 12/31/2022] [Accepted: 01/11/2023] [Indexed: 01/15/2023] Open
Abstract
Background: In patients with BD-IPMN, surgical indications have been focused on finding malignant lesions (HGD, high-grade dysplasia/IC, invasive carcinoma). The aim of this study was to compare the preoperative factors that distinguish HGD from LGD (low-grade dysplasia) and HGD from IC to find the optimal pathologic target for surgery according to individuals, considering surgical risks and outcomes. Methods: We retrospectively analyzed 232 patients with BD-IPMN diagnosed based on pathology after surgery and preoperative images. The primary outcome was identifying preoperative factors distinguishing HGD from LGD, and HGD from IC. Results: In patients with LGD/HGD, a solid component or an enhancing mural nodule ≥ 5 mm (OR = 9.29; 95% CI: 3.3−54.12; p < 0.000) and thickened/enhancing cyst walls (OR = 6.95; 95% CI: 1.68−33.13; p = 0.008) were associated with HGD. In patients with malignant lesions (HGD/IC), increased serum CA 19-9 (OR = 12.59; 95% CI: 1.81−87.44; p = 0.006) was associated with IC. Conclusions: The predictive factors for HGD were the presence of a solid component or an enhancing mural nodule ≥ 5 mm and thickened/enhancing cyst walls compared with LGD, and if accompanied by increased CA 19-9, it might be necessary to urgently evaluate the lesion due to the possibility of progression to IC. Based on this finding, we need to find HGD as the optimal pathologic target for surgery to improve survival in low-surgical-risk patients, and IC could be assumed to be the optimal pathologic target for surgery in high-surgical-risk patients because of high morbidity and mortality associated with surgery.
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Affiliation(s)
- Ji Eun Na
- Department of Medicine, Inje University Haeundae Paik Hospital, Busan 48108, Republic of Korea
| | - Jae Keun Park
- Department of Internal Medicine, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul 07441, Republic of Korea
| | - Jong Kyun Lee
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea
| | - Joo Kyung Park
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea
| | - Kwang Hyuck Lee
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea
- Department of Clinical Research Design and Evaluation, SAIHST, Sungkyunkwan University, Seoul 16419, Republic of Korea
| | - Kyu Taek Lee
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea
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Alwahbi O, Larocque N, Kulkarni A, Gopee-Ramanan PP, Ghumman Z, Sarkar R, Kagoma Y, Alabousi A, Tsai S, Wat J, McInnes M, van der Pol CB. Pancreatic Cystic Lesions on MRI: What Is The Likelihood of a Present or Future Diagnosis of Pancreatic Carcinoma? J Magn Reson Imaging 2022; 57:1567-1575. [PMID: 36151888 DOI: 10.1002/jmri.28438] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2022] [Revised: 09/07/2022] [Accepted: 09/07/2022] [Indexed: 11/09/2022] Open
Abstract
BACKGROUND Pancreatic cystic lesions (PCLs) are followed for years due to older and likely biased works demonstrating a strong association with pancreatic carcinoma; more recent data are needed clarifying this relationship. PURPOSE To determine the association between PCLs on MRI and a synchronous or future diagnosis of pancreatic carcinoma. STUDY TYPE Single-center retrospective cohort. POPULATION A total of 192 patients (111 female, 58%) with median age 66 years (range 26-87 years) with PCLs on abdominal MRI from 2011 to 2016. FIELD STRENGTH/SEQUENCES 1.5 T and 3 T, including T2 WI, T1 WI, diffusion weighted imaging and contrast-enhanced T1 WI. ASSESSMENT Each PCL was reviewed independently by 2 of 10 fellowship-trained abdominal radiologists. Fukuoka guideline worrisome features and high-risk stigmata were evaluated. Follow-up imaging and clinical notes were reviewed within a system that captures pancreatic carcinoma for the region, for a median follow-up of 67 months (interquartile range: 43-88 months). STATISTICAL TESTS Pancreatic carcinoma prevalence and incidence rate for future carcinoma with 95% confidence intervals (95% CI). Fisher exact test, logistic regression with odds ratios (OR) and the Wilcoxon rank-sum test were used to assess PCL morphologic features with the Kolmogorov-Smirnov test used to assess for normality. P < 0.05 defined statistical significance. RESULTS The prevalence of pancreatic carcinoma on initial MRI showing a PCL was 2.4% (95% CI: 0.9%, 5.2%). Thickened/enhancing cyst wall was associated with pancreatic carcinoma, OR 52 (95% CI: 4.5, 1203). Of 189 patients with a PCL but without pancreatic carcinoma at the time of initial MRI, one developed high-grade dysplasia and none developed invasive carcinoma for an incidence rate of 0.97 (95% CI: 0.02, 5.43) and 0 (95% CI: 0, 3.59) cases per 1000 person-years, respectively. DATA CONCLUSION A low percentage of patients with a PCL on MRI had a pancreatic carcinoma at the time of initial evaluation and none developed carcinoma over a median 67 months of follow-up. EVIDENCE LEVEL 3 TECHNICAL EFFICACY: 5.
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Affiliation(s)
- Omar Alwahbi
- Department of Radiology, Hamilton Health Sciences, McMaster University, Hamilton, Ontario, Canada
| | - Natasha Larocque
- Department of Radiology, Hamilton Health Sciences, McMaster University, Hamilton, Ontario, Canada.,Department of Diagnostic Imaging, Hamilton General Hospital, Hamilton Health Sciences, Hamilton, Ontario, Canada
| | - Ameya Kulkarni
- Department of Radiology, Hamilton Health Sciences, McMaster University, Hamilton, Ontario, Canada.,Department of Diagnostic Imaging, Juravinski Hospital and Cancer Centre, Hamilton Health Sciences, Hamilton, Ontario, Canada
| | - Prasaanthan Prasa Gopee-Ramanan
- Department of Radiology, Hamilton Health Sciences, McMaster University, Hamilton, Ontario, Canada.,Department of Diagnostic Imaging, Juravinski Hospital and Cancer Centre, Hamilton Health Sciences, Hamilton, Ontario, Canada
| | - Zonia Ghumman
- Department of Radiology, Hamilton Health Sciences, McMaster University, Hamilton, Ontario, Canada.,Department of Diagnostic Imaging, Juravinski Hospital and Cancer Centre, Hamilton Health Sciences, Hamilton, Ontario, Canada
| | - Rahul Sarkar
- Department of Radiology, Hamilton Health Sciences, McMaster University, Hamilton, Ontario, Canada.,Department of Diagnostic Imaging, Juravinski Hospital and Cancer Centre, Hamilton Health Sciences, Hamilton, Ontario, Canada
| | - Yoan Kagoma
- Department of Radiology, Hamilton Health Sciences, McMaster University, Hamilton, Ontario, Canada.,Department of Diagnostic Imaging, Juravinski Hospital and Cancer Centre, Hamilton Health Sciences, Hamilton, Ontario, Canada
| | - Abdullah Alabousi
- Department of Radiology, Hamilton Health Sciences, McMaster University, Hamilton, Ontario, Canada.,Department of Diagnostic Imaging, St. Joseph's Healthcare Hamilton, Hamilton, Ontario, Canada
| | - Scott Tsai
- Department of Radiology, Hamilton Health Sciences, McMaster University, Hamilton, Ontario, Canada.,Department of Diagnostic Imaging, Juravinski Hospital and Cancer Centre, Hamilton Health Sciences, Hamilton, Ontario, Canada
| | - Josephine Wat
- Department of Radiology, Hamilton Health Sciences, McMaster University, Hamilton, Ontario, Canada.,Department of Diagnostic Imaging, Juravinski Hospital and Cancer Centre, Hamilton Health Sciences, Hamilton, Ontario, Canada
| | - Matthew McInnes
- Department of Radiology and Epidemiology, University of Ottawa, Canada.,Ottawa Hospital Research Institute Clinical Epidemiology Program, Ontario, Canada
| | - Christian B van der Pol
- Department of Radiology, Hamilton Health Sciences, McMaster University, Hamilton, Ontario, Canada.,Department of Diagnostic Imaging, Juravinski Hospital and Cancer Centre, Hamilton Health Sciences, Hamilton, Ontario, Canada
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Xu Y, Xie C, Gao Z, Zhang M, Zhan M. Nomogram to predict malignancy in branch duct type intraductal papillary mucinous neoplasms. Medicine (Baltimore) 2022; 101:e30627. [PMID: 36197166 PMCID: PMC9509101 DOI: 10.1097/md.0000000000030627] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
Prediction of malignancy in branch duct (BD)-type intraductal papillary mucinous neoplasms (BD-IPMNs) is difficult. In this retrospective study, we showed the performance of imaging biomarker and biochemical biomarker in identifying the malignant BD-IPMNs. A total of 97 patients with pathological proved BD-IPMNs were included in this study. Imaging data were collected from magnetic resonance imaging (MRI). Malignant BD-IPMNs were defined as those with high grade dysplasia and invasive carcinoma. There were 10 patients with malignant BD-IPMNs (10.3%). Significant difference was found in prevalence of mural nodule and tumor size >3.0 cm between patients with and without malignant BD-IPMNs (44.4% vs 3.1%, P < .01; 80.0% vs 33.3%, P < .01). Significant differences were observed in mural nodule and elevated carbohydrate antigen 19-9 (CA19-9) between patients with and without invasive carcinoma (40.0% vs 7.6, P = .05; 60% vs 15.3%, P = .04). Mural nodule and tumor size >3.0 cm were the independent associated factor for malignant BD-IPMNs. The odds ratio (OR) was 5.22 (95% confidence interval [CI]: 1.04-31.16) for mural nodule and was 6.80 (95% CI: 1.16-39.71) for cyst size >3.0 cm. The combined model of mural nodule and tumor size showed good performance in identifying malignant BD-IPMNs (area under the curve [AUC] = 0.82, 95%CI: 0.67-0.97). Our data show that mural nodule and cystic size can be used as predictor of malignancy in BD-IPMN. The predictive performance is acceptable.
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Affiliation(s)
- Yisheng Xu
- Department of Radiology, Hangzhou Xiaoshan Hospital of Traditional Chinese Medicine, Hangzhou Zhenjiang, China
| | - Chunmei Xie
- Department of Radiology, Affiliated Xiaoshan Hospital, Hangzhou Normal University, Hangzhou Zhenjiang, China
| | - Zhiqin Gao
- Department of Radiology, Hangzhou Xiaoshan Hospital of Traditional Chinese Medicine, Hangzhou Zhenjiang, China
| | - Meihua Zhang
- Department of Radiology, Hangzhou Ninth People’s Hospital, Hangzhou Zhenjiang, China
| | - Ming Zhan
- Department of Radiology, Affiliated Xiaoshan Hospital, Hangzhou Normal University, Hangzhou Zhenjiang, China
- *Correspondence: Ming Zhan, Department of Radiology, Affiliated Xiaoshan Hospital, Hangzhou Normal University, No. 728 Yucai North Road, Xiaoshan District, Hangzhou Zhenjiang 311201, China (e-mail: )
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5
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Abstract
Early detection of high-risk pancreatic cystic lesions enables potentially curative surgical resection, and early detection of lesions without worrisome features may lead to appropriate surveillance. Regrettably, differentiating premalignant and malignant cysts from nonmalignant ones remains challenging. However, emerging additional diagnostic tools, including the needle biopsy with microforceps and needle-based confocal laser endomicroscopy, are of exciting potential along with cyst fluid analysis".
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Affiliation(s)
- Sahin Coban
- Department of Gastroenterology, Mount Auburn Hospital, 330 Mt Auburn St, Cambridge, MA 02138, USA.
| | - Omer Basar
- Department of Gastroenterology, The University of Missouri, Columbia, MO 65211, USA
| | - William R Brugge
- Department of Gastroenterology, Harvard Medical School, Mount Auburn Hospital, 330 Mt Auburn St, Cambridge, MA 02138, USA
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6
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Sotozono H, Kanki A, Yasokawa K, Yamamoto A, Sanai H, Moriya K, Tamada T. Value of 3-T MR imaging in intraductal papillary mucinous neoplasm with a concomitant invasive carcinoma. Eur Radiol 2022; 32:8276-8284. [PMID: 35665843 DOI: 10.1007/s00330-022-08881-6] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2022] [Revised: 04/26/2022] [Accepted: 05/12/2022] [Indexed: 11/30/2022]
Abstract
OBJECTIVES To examine the value of 3-T MRI for evaluating the difference between the pancreatic parenchyma of intraductal papillary mucinous neoplasm with a concomitant invasive carcinoma (IPMN-IC) and the pancreatic parenchyma of patients without an IPMN-IC. METHODS A total of 132 patients underwent abdominal 3-T MRI. Of the normal pancreatic parenchymal measurements, the pancreas-to-muscle signal intensity ratio in in-phase imaging (SIR-I), SIR in opposed-phase imaging (SIR-O), SIR in T2-weighted imaging (SIR-T2), ADC (×10-3 mm2/s) in DWI, and proton density fat fraction (PDFF [%]) in multi-echo 3D DIXON were calculated. The patients were divided into three groups (normal pancreas group: n = 60, intraductal papillary mucinous neoplasm (IPMN) group: n = 60, IPMN-IC group: n = 12). RESULTS No significant differences were observed among the three groups in age, sex, body mass index, prevalence of diabetes mellitus, and hemoglobin A1c (p = 0.141 to p = 0.657). In comparisons among the three groups, the PDFF showed a significant difference (p < 0.001), and there were no significant differences among the three groups in SIR-I, SIR-O, SIR-T2, and ADC (p = 0.153 to p = 0.684). The PDFF of the pancreas was significantly higher in the IPMN-IC group than in the normal pancreas group or the IPMN group (p < 0.001 and p < 0.001, respectively), with no significant difference between the normal pancreas group and the IPMN group (p = 0.916). CONCLUSIONS These observations suggest that the PDFF of the pancreas is associated with the presence of IPMN-IC. KEY POINTS • The cause and risk factors of IPMN with a concomitant invasive carcinoma have not yet been clarified. • The PDFF of the pancreas was significantly higher in the IPMN-IC group than in the normal pancreas group or the IPMN group. • Pancreatic PDFF may be a potential biomarker for the development of IPMN with a concomitant invasive carcinoma.
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Affiliation(s)
- Hidemitsu Sotozono
- Department of Radiology, Kawasaki Medical School, 577 Matsushima, Kurashiki city, Okayama, 701-0192, Japan.
| | - Akihiko Kanki
- Department of Radiology, Kawasaki Medical School, 577 Matsushima, Kurashiki city, Okayama, 701-0192, Japan
| | - Kazuya Yasokawa
- Department of Radiology, Kawasaki Medical School, 577 Matsushima, Kurashiki city, Okayama, 701-0192, Japan
| | - Akira Yamamoto
- Department of Radiology, Kawasaki Medical School, 577 Matsushima, Kurashiki city, Okayama, 701-0192, Japan
| | - Hiroyasu Sanai
- Department of Radiology, Kawasaki Medical School, 577 Matsushima, Kurashiki city, Okayama, 701-0192, Japan
| | - Kazunori Moriya
- Department of Radiology, Kawasaki Medical School, 577 Matsushima, Kurashiki city, Okayama, 701-0192, Japan
| | - Tsutomu Tamada
- Department of Radiology, Kawasaki Medical School, 577 Matsushima, Kurashiki city, Okayama, 701-0192, Japan
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Jung HS, Han Y, Kang JS, Sohn H, Lee M, Lee KB, Kim H, Kwon W, Jang JY. Prediction of malignancy in Main duct or Mixed-type Intraductal Papillary Mucinous Neoplasms of the Pancreas. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2022; 29:1014-1024. [PMID: 35451206 DOI: 10.1002/jhbp.1161] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/26/2021] [Revised: 02/20/2022] [Accepted: 03/27/2022] [Indexed: 11/10/2022]
Abstract
BACKGROUND/PURPOSE Surgical indications of main-duct involved intraductal papillary mucinous neoplasm (IPMN), especially for main pancreatic duct (MPD) of 5-9mm, remain controversial. We aimed to predict malignancy risk of main-duct involved IPMN. METHODS Total 258 patients with main-duct involved IPMN between 2000 and 2017 in our institute were retrospectively analyzed. Main-duct IPMN was classified into segmental and diffuse type by dilated MPD pattern. Clinicopathologic features and predictive factors for malignancy were analyzed. RESULTS Among 258, 47 and 211 had pure main-duct (segmental:27, diffuse-type:20) and mixed-type. Malignant IPMN presented higher in main-duct type (66.0%) compared to mixed-type (46.9%). The diffuse-type (72.2%) had more invasive carcinoma than the segmental type (40.7%). Invasive IPMN risk increased proportionally to the MPD diameter (5≤MPD <10mm vs. 10≤MPD<15mm vs. MPD≥15mm; 23.4% vs. 40.0% vs. 48.6%). Symptoms, elevated serum carbohydrate antigen, MPD ≥10mm, mural nodule, thickened wall, and distal atrophy were independent predictive factors for malignancy. Patients with MPD of 5-9mm with at least one predictive factor had 35.0% of malignancy risk. CONCLUSIONS The invasive IPMN risk was different according to the dilated main-duct pattern. Patients with main-duct type, diffuse-type, MPD ≥10mm, and MPD 5-9mm with at least one predictive factor should be candidates for immediate surgery.
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Affiliation(s)
- Hye-Sol Jung
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Youngmin Han
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Jae Seung Kang
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Heeju Sohn
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Mirang Lee
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Kyung-Bun Lee
- Department of Pathology, Seoul National University College of Medicine, Seoul, Korea
| | - Hongbeom Kim
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Wooil Kwon
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Jin-Young Jang
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
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Buerlein RCD, Shami VM. Management of pancreatic cysts and guidelines: what the gastroenterologist needs to know. Ther Adv Gastrointest Endosc 2021; 14:26317745211045769. [PMID: 34589706 PMCID: PMC8474323 DOI: 10.1177/26317745211045769] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2021] [Accepted: 08/25/2021] [Indexed: 12/15/2022] Open
Abstract
The prevalence of pancreatic cysts has increased significantly over the last
decade, partly secondary to increased quality and frequency of cross-sectional
imaging. While the majority never progress to cancer, a small number will and
need to be followed. The management of pancreatic cysts can be both confusing
and intimidating due to the multiple guidelines with varying recommendations.
Despite the differences in the specifics of the guidelines, they all agree on
several high-risk features that should get the attention of any clinician when
assessing a pancreatic cyst: presence of a mural nodule or solid component,
dilation of the main pancreatic duct (or presence of main duct intraductal
papillary mucinous neoplasm), pancreatic cyst size ⩾3–4 cm, or positive cytology
on pancreatic cyst fluid aspiration. Other important criteria to consider
include rapid cyst growth (⩾5 mm/year), elevated serum carbohydrate antigen 19-9
levels, new-onset diabetes mellitus, or acute pancreatitis thought to be related
to the cystic lesion.
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Affiliation(s)
| | - Vanessa M Shami
- University of Virginia Digestive Health, 1215 Lee Street, Charlottesville, VA 22903, USA
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9
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Automated Detection of Pancreatic Cystic Lesions on CT Using Deep Learning. Diagnostics (Basel) 2021; 11:diagnostics11050901. [PMID: 34069328 PMCID: PMC8158747 DOI: 10.3390/diagnostics11050901] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Revised: 05/03/2021] [Accepted: 05/14/2021] [Indexed: 12/21/2022] Open
Abstract
Pancreatic cystic lesions (PCL) are a frequent and underreported incidental finding on CT scans and can transform into neoplasms with devastating consequences. We developed and evaluated an algorithm based on a two-step nnU-Net architecture for automated detection of PCL on CTs. A total of 543 cysts on 221 abdominal CTs were manually segmented in 3D by a radiology resident in consensus with a board-certified radiologist specialized in abdominal radiology. This information was used to train a two-step nnU-Net for detection with the performance assessed depending on lesions' volume and location in comparison to three human readers of varying experience. Mean sensitivity was 78.8 ± 0.1%. The sensitivity was highest for large lesions with 87.8% for cysts ≥220 mm3 and for lesions in the distal pancreas with up to 96.2%. The number of false-positive detections for cysts ≥220 mm3 was 0.1 per case. The algorithm's performance was comparable to human readers. To conclude, automated detection of PCL on CTs is feasible. The proposed model could serve radiologists as a second reading tool. All imaging data and code used in this study are freely available online.
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10
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Shah R, Mulki R, Lamm V, Kapil N, Patel V, Chawla S, Cai Q, Willingham FF, Keilin S. Prevalence and Risk Factors for Intraductal Papillary Mucinous Neoplasm in Patients With Chronic Kidney Disease: A Single-Center Case-Control Study. Pancreas 2021; 50:327-329. [PMID: 33835962 DOI: 10.1097/mpa.0000000000001752] [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] [Indexed: 12/10/2022]
Abstract
OBJECTIVES The exact prevalence for intraductal papillary mucinous neoplasm (IPMN) in patients with chronic kidney disease (CKD) remains unknown. In this single-center case-control study, we aimed to study the prevalence and risk factors for IPMN in patients with CKD. METHODS We performed a retrospective case-control study comparing patients with and without CKD who had magnetic resonance imaging of the abdomen performed between January 2018 and December 2018. Patient demographic, clinical, and imaging metrics were extracted from chart review. The prevalence of IPMN was compared between the 2 groups. RESULTS A total of 800 patient charts were reviewed. There were 400 patients with CKD compared with an age-matched control group of 400 patients without CKD. The total prevalence of IPMN in patients with CKD was 13.7% (55/400) compared with 7.8% (29/400; P = 0.002) in non-CKD patients. The prevalence of diabetes mellitus was significantly higher in the CKD group (41% vs 14%, P = 0.0001). The percentage of patients consuming alcohol was significantly higher in the non-CKD group (23% vs 35%, P = 0.002). CONCLUSIONS Patients with CKD have a significantly higher prevalence of IPMN compared with non-CKD patients. Larger population-based studies are needed to confirm these findings.
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MESH Headings
- Adenocarcinoma, Mucinous/diagnosis
- Adenocarcinoma, Mucinous/diagnostic imaging
- Adenocarcinoma, Mucinous/epidemiology
- Adult
- Aged
- Aged, 80 and over
- Carcinoma, Pancreatic Ductal/diagnosis
- Carcinoma, Pancreatic Ductal/diagnostic imaging
- Carcinoma, Pancreatic Ductal/epidemiology
- Case-Control Studies
- Comorbidity
- Female
- Humans
- Magnetic Resonance Imaging/methods
- Male
- Middle Aged
- Pancreatic Neoplasms/diagnosis
- Pancreatic Neoplasms/diagnostic imaging
- Pancreatic Neoplasms/epidemiology
- Prevalence
- Renal Insufficiency, Chronic/diagnosis
- Renal Insufficiency, Chronic/diagnostic imaging
- Renal Insufficiency, Chronic/epidemiology
- Retrospective Studies
- Risk Assessment/methods
- Risk Assessment/statistics & numerical data
- Risk Factors
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Affiliation(s)
- Rushikesh Shah
- From the Division of Digestive Diseases, Emory University, Atlanta, GA
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Matsubayashi H, Ishiwatari H, Sasaki K, Uesaka K, Ono H. Detecting Early Pancreatic Cancer: Current Problems and Future Prospects. Gut Liver 2020; 14:30-36. [PMID: 31009958 PMCID: PMC6974337 DOI: 10.5009/gnl18491] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2018] [Revised: 01/05/2019] [Accepted: 01/25/2019] [Indexed: 12/13/2022] Open
Abstract
The number of patients with pancreatic cancer (PC) is currently increasing in both Korea and Japan. The 5-year survival rate of patients with PC 13.0%; however, resection with minimal invasion (tumor size: ≤10 mm) increases the 5-year survival rate to 80%. For this reason, early detection is essential, but most patients with early-stage PC are asymptomatic. Early detection of PC has been reported to require screening of high-risk individuals (HRIs), such as those with a family history of PC, inherited cancer syndromes, intraductal papillary mucinous neoplasm, or chronic pancreatitis. Studies on screening of these HRIs have confirmed a significantly better prognosis among patients with PC who were screened than for patients with PC who were not screened. However, to date in Japan, most patients with early-stage PC diagnosed in routine clinics were not diagnosed during annual health checks or by surveillance; rather, PC was detected in these patients by incidental findings during examinations for other diseases. We need to increase the precision of the PC screening and diagnostic processes by introducing new technologies, and we need to pay greater attention to incidental clinical findings.
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Affiliation(s)
- Hiroyuki Matsubayashi
- Division of Endoscopy, Shizuoka Cancer Center, Shizuoka, Japan.,Division of Genetic Medicine Promotion, Shizuoka Cancer Center, Shizuoka, Japan
| | | | - Keiko Sasaki
- Division of Pathology, Shizuoka Cancer Center, Shizuoka, Japan
| | - Katsuhiko Uesaka
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Shizuoka, Japan
| | - Hiroyuki Ono
- Division of Endoscopy, Shizuoka Cancer Center, Shizuoka, Japan
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12
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Park RHS, Lim GRS, Wu JJY, Koh YX, Teo JY, Cheow PC, Chan CY, Ooi LLPJ, Chung AYF, Goh BKP. Validation of the clinical utility of 4 guidelines in the initial triage of mucinous cystic lesions of the pancreas based on cross-sectional imaging: Experience with 188 surgically-treated patients. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2020; 46:2114-2121. [PMID: 32828582 DOI: 10.1016/j.ejso.2020.07.027] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2020] [Revised: 07/10/2020] [Accepted: 07/19/2020] [Indexed: 11/30/2022]
Abstract
INTRODUCTION Over the years, several guidelines have been introduced to guide management of mucinous pancreatic cystic neoplasms (mPCN). In this study, we aimed to evaluate and compare the clinically utility of the Sendai-06, Fukuoka-12, Fukuoka-17 and European-18 guidelines in predicting malignancy of mPCN. METHODS One hundred and eighty-eight patients with mucinous cystic neoplasms (MCN) or intraductal papillary mucinous neoplasm (IPMN) who underwent surgery were retrospectively reviewed and classified under the 4 guidelines. Malignancy was defined as high grade dysplasia and invasive carcinoma. RESULTS Raised CA19-9>37U/ml, enhancing mural nodule≥5 mm and main pancreatic duct≥10 mm were significantly associated with malignancy on multivariate analysis. Increasing number of high risk features, absolute indications (European-18), worrisome risk or relative indications (European-18) were significantly associated with an increased likelihood of malignancy. The positive predictive values (PPV) of high risk features for Sendai-06, Fukuoka-12, Fukuoka-17 and absolute indications (European-18) for malignancy were 53%, 76%, 78% and 78% respectively. The negative predictive values (NPV) of the Sendai-06, Fukuoka-12 and Fukuoka-17 were 100%, while that of the European-18 was 92%. Risk of malignancy for patients with ≥4 worrisome features (Fukuoka-17) and ≥3 relative indications (European-18) was 66.7% and 75.0% respectively. CONCLUSIONS All 4 guidelines studied were useful in the initial triage of mPCN for the risk stratification of malignancy. The Fukuoka-17 had the highest PPV and NPV.
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MESH Headings
- Adenocarcinoma, Mucinous/diagnostic imaging
- Adenocarcinoma, Mucinous/pathology
- Adenocarcinoma, Mucinous/physiopathology
- Adenocarcinoma, Mucinous/surgery
- Adult
- Aged
- Aged, 80 and over
- Biopsy, Fine-Needle
- CA-19-9 Antigen/metabolism
- Dilatation, Pathologic
- Female
- Humans
- Jaundice, Obstructive/physiopathology
- Lymphadenopathy/diagnostic imaging
- Male
- Middle Aged
- Neoplasms, Cystic, Mucinous, and Serous/diagnostic imaging
- Neoplasms, Cystic, Mucinous, and Serous/pathology
- Neoplasms, Cystic, Mucinous, and Serous/physiopathology
- Neoplasms, Cystic, Mucinous, and Serous/surgery
- Pancreatic Ducts/diagnostic imaging
- Pancreatic Intraductal Neoplasms/diagnostic imaging
- Pancreatic Intraductal Neoplasms/pathology
- Pancreatic Intraductal Neoplasms/physiopathology
- Pancreatic Intraductal Neoplasms/surgery
- Pancreatic Neoplasms/diagnostic imaging
- Pancreatic Neoplasms/pathology
- Pancreatic Neoplasms/physiopathology
- Pancreatic Neoplasms/surgery
- Pancreatitis/physiopathology
- Retrospective Studies
- Risk Assessment
- Triage
- Tumor Burden
- Young Adult
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Affiliation(s)
- Rachel H S Park
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Academia Level 5, 20 College Road, Singapore, 169856, Singapore; Yong Loo Lin School of Medicine, National University of Singapore, 10 Medical Drive, Singapore, 117597, Singapore
| | - Grace R S Lim
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Academia Level 5, 20 College Road, Singapore, 169856, Singapore; Yong Loo Lin School of Medicine, National University of Singapore, 10 Medical Drive, Singapore, 117597, Singapore
| | - Jania J Y Wu
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Academia Level 5, 20 College Road, Singapore, 169856, Singapore; Yong Loo Lin School of Medicine, National University of Singapore, 10 Medical Drive, Singapore, 117597, Singapore
| | - Ye-Xin Koh
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Academia Level 5, 20 College Road, Singapore, 169856, Singapore; Duke NUS Medical School, 8 College Road, Singapore, 169857, Singapore
| | - Jin-Yao Teo
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Academia Level 5, 20 College Road, Singapore, 169856, Singapore; Duke NUS Medical School, 8 College Road, Singapore, 169857, Singapore
| | - Peng-Chung Cheow
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Academia Level 5, 20 College Road, Singapore, 169856, Singapore; Duke NUS Medical School, 8 College Road, Singapore, 169857, Singapore
| | - Chung-Yip Chan
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Academia Level 5, 20 College Road, Singapore, 169856, Singapore; Duke NUS Medical School, 8 College Road, Singapore, 169857, Singapore
| | - London L P J Ooi
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Academia Level 5, 20 College Road, Singapore, 169856, Singapore; Duke NUS Medical School, 8 College Road, Singapore, 169857, Singapore
| | - Alexander Y F Chung
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Academia Level 5, 20 College Road, Singapore, 169856, Singapore; Duke NUS Medical School, 8 College Road, Singapore, 169857, Singapore
| | - Brian K P Goh
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Academia Level 5, 20 College Road, Singapore, 169856, Singapore; Duke NUS Medical School, 8 College Road, Singapore, 169857, Singapore.
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13
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Tobaly D, Santinha J, Sartoris R, Dioguardi Burgio M, Matos C, Cros J, Couvelard A, Rebours V, Sauvanet A, Ronot M, Papanikolaou N, Vilgrain V. CT-Based Radiomics Analysis to Predict Malignancy in Patients with Intraductal Papillary Mucinous Neoplasm (IPMN) of the Pancreas. Cancers (Basel) 2020; 12:cancers12113089. [PMID: 33114028 PMCID: PMC7690711 DOI: 10.3390/cancers12113089] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2020] [Revised: 10/17/2020] [Accepted: 10/21/2020] [Indexed: 02/07/2023] Open
Abstract
To assess the performance of CT-based radiomics analysis in differentiating benign from malignant intraductal papillary mucinous neoplasms of the pancreas (IPMN), preoperative scans of 408 resected patients with IPMN were retrospectively analyzed. IPMNs were classified as benign (low-grade dysplasia, n = 181), or malignant (high grade, n = 128, and invasive, n = 99). Clinicobiological data were reported. Patients were divided into a training cohort (TC) of 296 patients and an external validation cohort (EVC) of 112 patients. After semi-automatic tumor segmentation, PyRadiomics was used to extract radiomics features. A multivariate model was developed using a logistic regression approach. In the training cohort, 85/107 radiomics features were significantly different between patients with benign and malignant IPMNs. Unsupervised clustering analysis revealed four distinct clusters of patients with similar radiomics features patterns with malignancy as the most significant association. The multivariate model differentiated benign from malignant tumors in TC with an area under the ROC curve (AUC) of 0.84, sensitivity (Se) of 0.82, specificity (Spe) of 0.74, and in EVC with an AUC of 0.71, Se of 0.69, Spe of 0.57. This large study confirms the high diagnostic performance of preoperative CT-based radiomics analysis to differentiate between benign from malignant IPMNs.
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Affiliation(s)
- David Tobaly
- Service De Radiologie, Assistance Publique-Hôpitaux De Paris, APHP. Nord, Hôpital Beaujon, 92110 Clichy, France; (R.S.); (M.D.B.); (M.R.)
- Correspondence: (D.T.); (V.V.)
| | - Joao Santinha
- Computational Clinical Imaging Group, Champalimaud Research, Champalimaud Foundation, Avenida Brasília, 1400-038 Lisbon, Portugal;
- Instituto de Telecomunicações, Instituto Superior Técnico, University of Lisbon, 1049-001 Lisbon, Portugal
| | - Riccardo Sartoris
- Service De Radiologie, Assistance Publique-Hôpitaux De Paris, APHP. Nord, Hôpital Beaujon, 92110 Clichy, France; (R.S.); (M.D.B.); (M.R.)
- Centre De Recherche De L’inflammation (Cri), Inserm U1149, Université De Paris, 75018 Paris, France
| | - Marco Dioguardi Burgio
- Service De Radiologie, Assistance Publique-Hôpitaux De Paris, APHP. Nord, Hôpital Beaujon, 92110 Clichy, France; (R.S.); (M.D.B.); (M.R.)
- Centre De Recherche De L’inflammation (Cri), Inserm U1149, Université De Paris, 75018 Paris, France
| | - Celso Matos
- Radiology Department, Champalimaud Foundation, Avenida Brasília, 1400-038 Lisbon, Portugal;
- Champalimaud Research, Champalimaud Foundation, Avenida Brasília, 1400-038 Lisbon, Portugal
| | - Jérôme Cros
- Service D’Anatomopathologie, Assistance Publique-Hôpitaux De Paris, APHP.Nord, Hôpital Beaujon, 92110 Clichy, France;
| | - Anne Couvelard
- Service D’Anatomopathologie, Assistance Publique-Hôpitaux De Paris, APHP.Nord, Hôpital Bichat, 75018 Paris, France;
| | - Vinciane Rebours
- Service De Pancréatologie, Assistance Publique-Hôpitaux De Paris, APHP.Nord, Hôpital Beaujon, 92110 Clichy, France;
| | - Alain Sauvanet
- Service De Chirurgie HPB, Assistance Publique-Hôpitaux De Paris, APHP.Nord, Hôpital Beaujon, 92110 Clichy, France;
| | - Maxime Ronot
- Service De Radiologie, Assistance Publique-Hôpitaux De Paris, APHP. Nord, Hôpital Beaujon, 92110 Clichy, France; (R.S.); (M.D.B.); (M.R.)
- Centre De Recherche De L’inflammation (Cri), Inserm U1149, Université De Paris, 75018 Paris, France
| | - Nikolaos Papanikolaou
- Computational Clinical Imaging Group, Champalimaud Research, Champalimaud Foundation, 1400-038 Lisbon, Portugal;
| | - Valérie Vilgrain
- Service De Radiologie, Assistance Publique-Hôpitaux De Paris, APHP. Nord, Hôpital Beaujon, 92110 Clichy, France; (R.S.); (M.D.B.); (M.R.)
- Centre De Recherche De L’inflammation (Cri), Inserm U1149, Université De Paris, 75018 Paris, France
- Correspondence: (D.T.); (V.V.)
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An integrated analysis of host- and tumor-derived markers for predicting high-grade dysplasia and associated invasive carcinoma of intraductal papillary mucinous neoplasms of the pancreas. Surg Today 2020; 50:1039-1048. [PMID: 32124086 DOI: 10.1007/s00595-020-01982-z] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2019] [Accepted: 02/11/2020] [Indexed: 02/07/2023]
Abstract
PURPOSE To clarify the usefulness of cancer-related inflammation, hypermetabolism, and subsequent host malnutrition biomarkers for predicting the histological grades of intraductal papillary mucinous neoplasms of the pancreas (IPMNs). METHODS The systemic immune-inflammation index (SII), prognostic nutritional index (PNI), and maximum standardized uptake value (SUVmax) on fluorodeoxyglucose-positron emission tomography were compared across 171 resected IPMN cases of different histological grades. The diagnostic performance of each marker and of their combinations for predicting IPMN with high-grade dysplasia (HGD)/associated invasive carcinoma (INV) was also tested. RESULTS Of the 171 IPMNs, the IPMN cases with HGD showed significantly higher values of SII (median 406 vs. 340; P = 0.041) and SUVmax (median 2.5 vs. 2.0; P = 0.001) than those with low-grade dysplasia (LGD). On a multivariate analysis, the SII and SUVmax were both independent markers for predicting HGD/INV. A combination analysis including the tumor- and host-derived markers in combination with imaging findings showed an improved diagnostic performance (area under the curve 0.824; sensitivity 75.9%; specificity 80.0%). CONCLUSIONS The combination of multiple markers of host-derived inflammation and tumor-derived focal hypermetabolism can serve as a predictor for the presence of HGD/INV.
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15
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Recurrence patterns after surgical resection of intraductal papillary mucinous neoplasm (IPMN) of the pancreas; a multicenter, retrospective study of 1074 IPMN patients by the Japan Pancreas Society. J Gastroenterol 2020; 55:86-99. [PMID: 31463655 DOI: 10.1007/s00535-019-01617-2] [Citation(s) in RCA: 63] [Impact Index Per Article: 12.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2019] [Accepted: 08/08/2019] [Indexed: 02/04/2023]
Abstract
BACKGROUND Although there are numerous reports focusing on surgical indication for intraductal papillary mucinous neoplasm (IPMN), the recurrence patterns following surgery are less widely reported. To ascertain optimal treatment and postoperative surveillance for IPMN patients, we analyzed patterns and risk factors for recurrence after surgery for IPMN. METHODS This study is a retrospective, multi-institutional, observational study, including 1074 patients undergoing surgery for IPMN at 11 academic institutions. We analyzed the risk factors for recurrence after classifying postoperative recurrences into metachronous high-risk lesions (malignant progression of IPMN and/or metachronous pancreatic ductal adenocarcinoma) in the remnant pancreas and extra-pancreatic recurrence. RESULTS Of 1074 patients undergoing surgery for IPMN, 155 patients (14.4%) developed postoperative recurrence. We found that 34.3% of 70 high-risk lesions in the remnant pancreas occurred over 5 years after surgery, and survival of 36 patients undergoing second operation for high-risk lesions was better than that of 34 patients who did not (P = 0.04). We found four independent risk factors for metachronous high-risk lesions in remnant pancreas: symptoms [P = 0.005, hazard ratio (HR) 1.988], location of pancreatic body/tail (P < 0.001, HR 3.876), main duct size ≥ 10 mm (P = 0.021, HR 1.900), and high-grade dysplasia/invasive intraductal papillary mucinous carcinoma (IPMC) (P < 0.001, HR 3.204). Although six patients (0.7%) with low- or high-grade dysplasia IPMN developed extra-pancreatic recurrence, invasive IPMC was the strongest risk factor for extra-pancreatic recurrence (P < 0.001, HR 39.667). CONCLUSION We suggest that life-time continuous surveillance might be necessary for IPMN patients. Second surgery for metachronous high-risk lesions in remnant pancreas should be considered to improve survival.
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16
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Kawakami S, Fukasawa M, Shimizu T, Ichikawa S, Sato T, Takano S, Kadokura M, Shindo H, Takahashi E, Hirose S, Fukasawa Y, Hayakawa H, Nakayama Y, Yamaguchi T, Inoue T, Maekawa S, Kawaida H, Motosugi U, Onishi H, Enomoto N. Diffusion-weighted image improves detectability of magnetic resonance cholangiopancreatography for pancreatic ductal adenocarcinoma concomitant with intraductal papillary mucinous neoplasm. Medicine (Baltimore) 2019; 98:e18039. [PMID: 31764824 PMCID: PMC6882617 DOI: 10.1097/md.0000000000018039] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
The present study is aimed to clarify the utility of magnetic resonance cholangiopancreatography (MRCP) and the additional value of diffusion-weighted imaging (DWI) in diagnosing pancreatic ductal adenocarcinoma (PDAC) concomitant with intraductal papillary mucinous neoplasm (IPMN).This retrospective study involved 38 patients with PDAC concomitant with IPMN and 114 patients (control) who were randomly selected from 320 patients with IPMN without PDAC and were matched with cases for magnetic resonance imaging (MRI) strength (1.5 T/3.0 T). Two radiologists reviewed the 2 MR image sets with relevant clinical information blinded, first MRCP alone and then combined MRI set including DWI. Diagnostic capability and interobserver agreement were assessed by using receiver operating characteristics curve (Az) analysis and weighted κ statistics.Az values for the 2 observers were 0.834 and 0.821 for MRCP alone and 0.964 and 0.926 for the combined MRI (P < .001 and P < .001), respectively. The sensitivity of MRCP alone was 61% (23/38), with both observers failing to diagnose PDACs located at the end of tail or away from the pancreatic duct. Meanwhile, with combined MRI, sensitivity was significantly increased for both observers (61% to 92%, P = .002; 61% to 87%, P = .004). Moreover, the interobserver agreement was higher with combined MRI (κ = 0.85) than MRCP alone (κ = 0.59).MRCP and DWI might be a superior option with a higher diagnostic capability of PDAC concomitant with IPMN than MRCP alone, especially for tumors away from the pancreatic duct.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | - Hiromichi Kawaida
- First Department of Surgery, Faculty of Medicine, University of Yamanashi; 1110 Shimokato, Chuo, Yamanashi, Japan
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17
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van Huijgevoort NCM, Del Chiaro M, Wolfgang CL, van Hooft JE, Besselink MG. Diagnosis and management of pancreatic cystic neoplasms: current evidence and guidelines. Nat Rev Gastroenterol Hepatol 2019; 16:676-689. [PMID: 31527862 DOI: 10.1038/s41575-019-0195-x] [Citation(s) in RCA: 153] [Impact Index Per Article: 25.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 07/31/2019] [Indexed: 12/11/2022]
Abstract
Pancreatic cystic neoplasms (PCN) are a heterogeneous group of pancreatic cysts that include intraductal papillary mucinous neoplasms, mucinous cystic neoplasms, serous cystic neoplasms and other rare cystic lesions, all with different biological behaviours and variable risk of progression to malignancy. As more pancreatic cysts are incidentally discovered on routine cross-sectional imaging, optimal surveillance for patients with PCN is becoming an increasingly common clinical problem, highlighting the need to balance cancer prevention with the risk of (surgical) overtreatment. This Review summarizes the latest developments in the diagnosis and management of PCN, including the quality of available evidence. Also discussed are the most important differences between the PCN guidelines from the American Gastroenterological Association, the International Association of Pancreatology and the European Study Group on Cystic Tumours of the Pancreas, including diagnostic and follow-up strategies and indications for surgery. Finally, new developments in the management of patients with PCN are addressed.
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Affiliation(s)
- Nadine C M van Huijgevoort
- Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology and Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands
| | - Marco Del Chiaro
- Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Christopher L Wolfgang
- Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Jeanin E van Hooft
- Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology and Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands
| | - Marc G Besselink
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.
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18
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Laquière A, Lagarde A, Napoléon B, Bourdariat R, Atkinson A, Donatelli G, Pol B, Lecomte L, Curel L, Urena-Campos R, Helbert T, Valantin V, Mithieux F, Buono JP, Grandval P, Olschwang S. Genomic profile concordance between pancreatic cyst fluid and neoplastic tissue. World J Gastroenterol 2019; 25:5530-5542. [PMID: 31576098 PMCID: PMC6767987 DOI: 10.3748/wjg.v25.i36.5530] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2019] [Revised: 07/16/2019] [Accepted: 08/19/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND DNA mutational analysis of pancreatic cystic fluid (CF) is a useful adjunct to the evaluation of pancreatic cysts. KRAS/GNAS or RAF/PTPRD/CTNNB1/RNF43 mutations are highly specific to precancerous or advanced neoplasia. Several studies recently demonstrated the ability of next-generation sequencing (NGS) analysis to detect DNA mutations in pancreatic CF, but few studies have performed a systematic comparative analysis between pancreatic CF and neoplastic surgical tissue (NT). The value of CF-NGS analysis indicators for determining surgical resection necessitates evaluation.
AIM To confirm whether CF genomic profiles are a reliable malignancy predictor by comparing NGS mutational analyses of CF and NT.
METHODS Patients requiring surgery for high-risk pancreatic cysts were included in a multicenter prospective pilot study. DNA from CF (collected by endoscopic ultrasound-guided fine needle aspiration (known as EUS-FNA)) and NT (collected by surgery) were analyzed by NGS. The primary objective was to compare the mutation profiles of paired DNA samples. The secondary objective was to correlate the presence of specific mutations (KRAS/GNAS, RAF/ PTPRD/CTNNB1/RNF43/POLD1/TP53) with a final cancer diagnosis. Sensitivity and specificity were also evaluated.
RESULTS Between December 2016 and October 2017, 20 patients were included in this pilot study. Surgery was delayed for 3 patients. Concordant CF-NT genotypes were found in 15/17 paired DNA, with a higher proportion of mutated alleles in CF than in NT. NGS was possible for all pancreatic CF collected by EUS-FNA. In 2 cases, the presence of a KRAS/GNAS mutation was discordant between CF and NT. No mutations were found in 3 patients with NT or pancreatic cysts with high-grade dysplasia. The sensitivity and specificity of KRAS/GNAS mutations in CF to predict an appropriate indication for surgical resection were 0.78 and 0.62, respectively. The sensitivity and specificity of RAF/PTPRD/CTNNB1 /RNF43/POLD1/TP53 mutations in CF were 0.55 and 1.0, respectively.
CONCLUSION Mutational analyses of CF and NT were highly concordant, confirming the value of NGS analysis of CF in the preoperative malignancy assessment. However, these results need to be confirmed on a larger scale.
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Affiliation(s)
- Arthur Laquière
- Department of Gastroenterology, Saint Joseph Hospital, Marseille 13008, France
| | - Arnaud Lagarde
- Aix-Marseille Univ, INSERM, MMG, Marseille 13385, France
- AP-HM, Conception Hospital, Marseille 13385, France
| | | | | | | | | | - Bernard Pol
- Department of Digestive Surgery, Saint-Joseph Hospital, Marseille 13008, France
| | - Laurence Lecomte
- Department of Gastroenterology, Saint Joseph Hospital, Marseille 13008, France
| | - Laurence Curel
- Department of Clinical Research, Saint Joseph Hospital, Marseille 13008, France
| | - Romina Urena-Campos
- Department of Gastroenterology, Saint Joseph Hospital, Marseille 13008, France
| | | | | | | | | | - Philippe Grandval
- Aix-Marseille Univ, INSERM, MMG, Marseille 13385, France
- AP-HM, Timone Hospital, Marseille 13005, France
| | - Sylviane Olschwang
- Aix-Marseille Univ, INSERM, MMG, Marseille 13385, France
- European Hospital, Marseille 13003, France
- AP-HM, Timone Hospital, Marseille 13005, France
- RGDS, Clairval Hospital, Marseille 13009, France
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19
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Kang JS, Park T, Han Y, Lee S, Lim H, Kim H, Kim SH, Kwon W, Kim SW, Jang JY. Clinical validation of the 2017 international consensus guidelines on intraductal papillary mucinous neoplasm of the pancreas. Ann Surg Treat Res 2019; 97:58-64. [PMID: 31388508 PMCID: PMC6669133 DOI: 10.4174/astr.2019.97.2.58] [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: 05/02/2019] [Revised: 05/03/2019] [Accepted: 06/26/2019] [Indexed: 12/24/2022] Open
Abstract
Purpose The 2017 international consensus guidelines (ICG) for intraductal papillary mucinous neoplasm (IPMN) of the pancreas were recently released. Important changes included the addition of worrisome features such as elevated serum CA 19-9 and rapid cyst growth (>5 mm over 2 years). We aimed to clinically validate the 2017 ICG and compare the diagnostic performance between the 2017 and 2012 ICG. Methods This was a retrospective cohort study. During January 2000–January 2017, patients who underwent complete surgical resection and had pathologic confirmation of branch-duct or mixed-type IPMN were included. To evaluate diagnostic performance, the areas under the receiver operating curves (AUCs) were evaluated. Results A total of 448 patients were included. The presence of mural nodule (hazard ratio [HR], 9.12; 95% confidence interval [CI], 4.60–18.09; P = 0.001), main pancreatic duct dilatation (>5 mm) (HR, 5.32; 95% CI, 2.67–10.60; P = 0.001), thickened cystic wall (HR, 3.40; 95% CI, 1.51–7.63; P = 0.003), and elevated CA 19-9 level (>37 unit/mL) (HR, 5.25; 95% CI, 2.05–13.42; P = 0.001) were significantly associated with malignant IPMN. Malignant lesions showed a cyst growth rate >5 mm over 2 years more frequently than benign lesions (60.9% vs. 29.7%, P = 0.012). The AUC was higher for the 2017 ICG than the 2012 ICG (0.784 vs. 0.746). Conclusion The new 2017 ICG for IPMN is clinically valid, with a superior diagnostic performance to the 2012 ICG. The inclusion of elevated serum CA 19-9 level and cyst growth rate to the 2017 ICG is appropriate.
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Affiliation(s)
- Jae Seung Kang
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Taesung Park
- Department of Statistics and Interdisciplinary Program in Biostatistics, Seoul National University, Seoul, Korea
| | - Youngmin Han
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Seungyeon Lee
- Department of Mathematics and Statistics, Sejong University, Sejong, Korea
| | - Heeju Lim
- Department of Mathematics and Statistics, Sejong University, Sejong, Korea
| | - Hyeongseok Kim
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Se Hyung Kim
- Department of Radiology, Seoul National University College of Medicine, Seoul, Korea
| | - Wooil Kwon
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Sun-Whe Kim
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Jin-Young Jang
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
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Abstract
Intraductal papillary mucinous neoplasm (IPMN) is the most common pancreatic cystic neoplasm (PCN). The increased attention to IPMN is due to its unique features of malignant progression, being different between main duct IPMN and branch duct IPMN, and increased de novo development of conventional pancreatic ductal adenocarcinoma elsewhere in the pancreas. The increased interest in IPMN led to publication of many guidelines on its clinical management. This chapter aims to summarize and compare characteristics of nine guidelines on the clinical management of IPMN and other PCNs published in the English literature and further to show a current strategy for surgical decision making in the management of IPMN.
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Affiliation(s)
- Masao Tanaka
- Shimonoseki City Hospital, Kyushu University, Shimonoseki, Yamaguchi, Japan.
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21
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Intraductal Papillary Mucinous Neoplasm of the Pancreas as the Main Focus for Early Detection of Pancreatic Adenocarcinoma. Pancreas 2018; 47:544-550. [PMID: 29702531 DOI: 10.1097/mpa.0000000000001047] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
For early detection of pancreatic cancer, interests are now focused on the detection of high-risk individuals to undergo screening examinations. Intraductal papillary mucinous neoplasm (IPMN) is a unique dual precursor of pancreatic cancer, characterized by progression to invasive cancer and the development of pancreatic adenocarcinoma either concomitantly (synchronous occurrence) or even after resection of IPMN (metachronous occurrence). Careful examination and surveillance of patients with IPMN may therefore lead to early detection of pancreatic cancer. By reviewing only reports describing detailed breakdown of the morphological types of IPMN and numbers of patients with noninvasive and invasive carcinoma in each type, the rough frequencies of noninvasive carcinoma in main duct IPMNs and branch duct IPMNs (BD-IPMNs) are 20% and 10%, respectively, and those of invasive carcinoma are 40% and 13%, respectively. Roughly 5% of all patients with IPMN had concomitant adenocarcinoma. The real frequency of carcinoma in BD-IPMNs would be far lower because most patients with small asymptomatic BD-IPMNs do not undergo resection. Intraductal papillary mucinous neoplasm can be the main focus for early detection of pancreatic cancer to achieve favorable prognosis after surgical resection. The optimal protocol for surveillance and method for early detection of pancreatic cancer are to be determined.
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Hoshi H, Zaheer A, El Abiad RG, Maxwell JE, Chu LC, Gerke H, Chan CH. Management of pancreatic intraductal papillary mucinous neoplasm. Curr Probl Surg 2018; 55:126-152. [DOI: 10.1067/j.cpsurg.2018.03.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2018] [Accepted: 03/11/2018] [Indexed: 12/16/2022]
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Tanaka M. Intraductal Papillary Mucinous Neoplasm as the Focus for Early Detection of Pancreatic Cancer. Gastroenterology 2018; 154:475-478. [PMID: 29337154 DOI: 10.1053/j.gastro.2018.01.014] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Affiliation(s)
- Masao Tanaka
- Department of Surgery, Shimonoseki City Hospital, Shimonoseki, Japan.
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24
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Zhou W, Xu Y, Rong Y, Wu W, Kuang T, Xin B, Zhu H, Lou W, Wang D. Validation of Sendai and Fukuoka consensus guidelines in predicting malignancy in patients with preoperatively diagnosed mucinous pancreatic cystic neoplasms. J Surg Oncol 2017; 117:409-416. [PMID: 29044541 DOI: 10.1002/jso.24882] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2017] [Accepted: 09/18/2017] [Indexed: 01/04/2023]
Affiliation(s)
- Wentao Zhou
- Department of General Surgery, Zhong Shan Hospital, Fudan University, Shanghai, China
| | - Yadong Xu
- Department of Pancreatic Surgery, Zhong Shan Hospital, Fudan University, Shanghai, China
| | - Yefei Rong
- Department of General Surgery, Zhong Shan Hospital, Fudan University, Shanghai, China
| | - Wenchuan Wu
- Department of Pancreatic Surgery, Zhong Shan Hospital, Fudan University, Shanghai, China
| | - Tiantao Kuang
- Department of General Surgery, Zhong Shan Hospital, Fudan University, Shanghai, China
| | - Baobao Xin
- Department of General Surgery, Zhong Shan Hospital, Fudan University, Shanghai, China
| | - Hongxu Zhu
- Department of General Surgery, Zhong Shan Hospital, Fudan University, Shanghai, China
| | - Wenhui Lou
- Department of Pancreatic Surgery, Zhong Shan Hospital, Fudan University, Shanghai, China
| | - Dansong Wang
- Department of General Surgery, Zhong Shan Hospital, Fudan University, Shanghai, China
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25
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Impact of MUC1 Expression on the Progression of Intraductal Papillary Mucinous Neoplasm With Worrisome Features During Follow-up. Pancreas 2017; 46:1127-1132. [PMID: 28902782 DOI: 10.1097/mpa.0000000000000902] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
OBJECTIVES The aim of this study was to investigate whether MUC1 expression is associated with progression of intraductal papillary mucinous neoplasms with worrisome features during follow-up. METHODS Fifteen patients positive for MUC1 and negative for MUC2 (MUC1 group) and 16 patients negative for MUC1 and MUC2 (control group) were followed up and examined for changes in diameters of the main and ectatic branches of pancreatic ducts, enlargement of mural nodules, and appearance of a solid mass, by imaging studies. All of them presented worrisome features, and none had "high-risk stigmata." RESULTS The sizes of the main and ectatic branches of pancreatic ducts increased in 8 (53.3%) and 8 (53.3%) patients, respectively, of the MUC1 group and in 1 (6.3%) and 1 (6.3%) patients, respectively, of the control group (P = 0.0059 and 0.0059, respectively). A solid mass developed in 6 patients (33.3%) of the MUC1 group but in none of the control group patients (P = 0.0373). CONCLUSIONS Positive MUC1 expression in cell block cytology specimens may be associated with progressive dilation of the main and ectatic branches of pancreatic ducts and appearance of a solid mass in patients with intraductal papillary mucinous neoplasm with worrisome features during follow-up.
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26
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Lensing RJ, Bipat S. Incidences of Pancreatic Malignancy and Mortality in Patients With Untreated Branch-Duct Intraductal Papillary Mucinous Neoplasms Undergoing Surveillance: A Systematic Review. Pancreas 2017; 46:1098-1110. [PMID: 28902778 DOI: 10.1097/mpa.0000000000000907] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVE The aim of this study was to pool incidences of increased cyst size, malignant branch-duct intraductal papillary mucinous neoplasms (BD-IPMNs), pancreatic malignancy, and pancreatic malignancy-related death during follow-up (FU) of BD-IPMN patients. METHODS Searches were performed from January 2010 to April 2016. All hits were checked on inclusion criteria, and outcomes were extracted. Incidences were pooled. Three subgroups were defined: (1) including only BD-IPMN patients, (2) short-interval FU (maximum 6 months), and (3) long-interval FU (>6 months). RESULTS Thirty-one articles were enrolled, including 8455 patients (mean age, 66.4 years). Twenty-two studies included subgroup 1; 10 and 6 studies included, respectively, subgroups 2 and 3. Incidence of increased cyst size was 17.4%. In subgroups 1, 2, and 3, incidences were, respectively, 20.0%, 17.2%, and 31.7%. Incidence of malignant BD-IPMN was 2.5. In subgroups 1, 2, and 3, incidences were, respectively, 3.0%, 2.4%, and 3.3%. Incidence of pancreatic malignancy was 2.6%. In subgroups 1, 2, and 3, incidences were, respectively, 2.3%, 1.2%, and 4.0%. Incidence of death was 0.5%. In subgroups 1, 2, and 3, incidences were, respectively, 0.4%, 0.04%, and 0.12%. CONCLUSIONS Although not significant, all incidences on long-interval FU were higher; therefore, short-interval FU seems necessary to find resectable lesions.
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Affiliation(s)
- Rutger J Lensing
- From the Department of Radiology, Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands
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27
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Aronsson L, Andersson R, Ansari D. Intraductal papillary mucinous neoplasm of the pancreas - epidemiology, risk factors, diagnosis, and management. Scand J Gastroenterol 2017; 52:803-815. [PMID: 28446039 DOI: 10.1080/00365521.2017.1318948] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2017] [Revised: 04/05/2017] [Accepted: 04/09/2017] [Indexed: 02/04/2023]
Abstract
Intraductal papillary mucinous neoplasm (IPMN) is one of the most common cystic neoplasms of the pancreas. It is a heterogeneous disease and can be divided into ductal types and morphological subtypes. The incidence of IPMN is increasing, likely due to the widespread use of cross-sectional imaging and a growing elderly population. IPMN poses an increasing demand on the health care system. Current guidelines provide indications for surgery and recommendations for surveillance, but management of IPMN is still challenging in routine clinical practice. In this article, we review current knowledge about IPMN and provide future directions for improving diagnosis and management.
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MESH Headings
- Adenocarcinoma, Mucinous/diagnosis
- Adenocarcinoma, Mucinous/pathology
- Adenocarcinoma, Mucinous/therapy
- Carcinoma, Pancreatic Ductal/diagnosis
- Carcinoma, Pancreatic Ductal/pathology
- Carcinoma, Pancreatic Ductal/therapy
- Carcinoma, Papillary/diagnosis
- Carcinoma, Papillary/pathology
- Carcinoma, Papillary/therapy
- Diagnosis, Differential
- Genetic Predisposition to Disease
- Health Knowledge, Attitudes, Practice
- Humans
- Neoadjuvant Therapy
- Neoplasm Invasiveness
- Neoplasm Staging
- Pancreas/pathology
- Pancreatectomy
- Pancreatic Neoplasms/diagnosis
- Pancreatic Neoplasms/pathology
- Pancreatic Neoplasms/therapy
- Practice Guidelines as Topic
- Risk Factors
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Affiliation(s)
- Linus Aronsson
- a Department of Clinical Sciences Lund, Surgery , Lund University, Skane University Hospital , Lund , Sweden
| | - Roland Andersson
- a Department of Clinical Sciences Lund, Surgery , Lund University, Skane University Hospital , Lund , Sweden
| | - Daniel Ansari
- a Department of Clinical Sciences Lund, Surgery , Lund University, Skane University Hospital , Lund , Sweden
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28
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Lee T, Kim HJ, Park SK, Yang HJ, Jung YS, Park JH, Park DI, Cho YK, Sohn CI, Jeon WK, Kim BI, Choi KY. Natural courses of branch duct intraductal papillary mucinous neoplasm. Langenbecks Arch Surg 2017; 402:429-437. [PMID: 28255733 DOI: 10.1007/s00423-017-1565-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2016] [Accepted: 02/08/2017] [Indexed: 01/09/2023]
Abstract
PURPOSE The study was done to elucidate the clinico-radiologic predictive factors for cancerous change detected by disease progression (PD) mainly defined by interval increase in cyst size and change of cyst morphology, for branch duct intraductal papillary mucinous neoplasm (BD-IPMN) patients with relatively long-term follow-up. METHODS Retrospective analysis of medical records and imaging findings were performed on 107 patients with BD-IPMN enrolled from July 2005 to May 2013, in whom the communication between the cystic lesion and pancreatic duct was confirmed by either endoscopic ultrasonography (EUS), magnetic resonance cholangiopancreatography (MRCP), or endoscopic retrograde cholangiopancreatography (ERCP). RESULTS During the mean ± SD follow-up period of 51.5 ± 24.5 months, PD was noticed in 43 (40.2%) of 107 BD-IPMN patients. Among these 107 patients, 21 (19.6%) displayed cancerous change. By univariate analyses, septated/multilocular cyst morphology, cyst size larger than 30 mm, cyst wall thickening, mural nodules, and the presence of symptoms were significant predictive factors for cancerous changes in BD-IPMN patients. A Cox forward stepwise linear regression model revealed that cyst wall thickening (OR 9.187, 95% CI 1.883~44.820, P < 0.01) and mural nodules (OR 6.224, 95% CI 1.311~29.549, P = 0.021) were significant and independent predictive factors for cancerous change in BD-IPMN patients. CONCLUSIONS A significant proportion of patients with BD-IPMN showed PD and cancerous change during the long-term follow-up. Cyst wall thickening and mural nodules were significant and independent predictive factors of cancerous change in patients with BD-IPMN.
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Affiliation(s)
- Taeheon Lee
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 29, Saemunan-Ro, Jongno-Gu, Seoul, 03181, Republic of Korea
| | - Hong Joo Kim
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 29, Saemunan-Ro, Jongno-Gu, Seoul, 03181, Republic of Korea.
| | - Soo-Kyung Park
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 29, Saemunan-Ro, Jongno-Gu, Seoul, 03181, Republic of Korea
| | - Hyo-Joon Yang
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 29, Saemunan-Ro, Jongno-Gu, Seoul, 03181, Republic of Korea
| | - Yoon Suk Jung
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 29, Saemunan-Ro, Jongno-Gu, Seoul, 03181, Republic of Korea
| | - Jung Ho Park
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 29, Saemunan-Ro, Jongno-Gu, Seoul, 03181, Republic of Korea
| | - Dong Il Park
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 29, Saemunan-Ro, Jongno-Gu, Seoul, 03181, Republic of Korea
| | - Yong Kyun Cho
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 29, Saemunan-Ro, Jongno-Gu, Seoul, 03181, Republic of Korea
| | - Chong Il Sohn
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 29, Saemunan-Ro, Jongno-Gu, Seoul, 03181, Republic of Korea
| | - Woo Kyu Jeon
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 29, Saemunan-Ro, Jongno-Gu, Seoul, 03181, Republic of Korea
| | - Byung Ik Kim
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 29, Saemunan-Ro, Jongno-Gu, Seoul, 03181, Republic of Korea
| | - Kyu Yong Choi
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 29, Saemunan-Ro, Jongno-Gu, Seoul, 03181, Republic of Korea
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Hanada K, Amano H, Abe T. Early diagnosis of pancreatic cancer: Current trends and concerns. Ann Gastroenterol Surg 2017; 1:44-51. [PMID: 29863166 PMCID: PMC5881352 DOI: 10.1002/ags3.12004] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2016] [Accepted: 02/15/2017] [Indexed: 12/27/2022] Open
Abstract
Early detection of pancreatic cancer (PC) is essential for a better prognosis. Some recent studies have demonstrated that a slight dilatation of the main pancreatic duct (MPD) and small cystic lesions were detected initially in most cases diagnosed at an early stage. Detecting these abnormal findings in cases with high risk factors through an effective screening system including image diagnosis, some biological markers, or familial cancer registrations should contribute to early diagnosis of PC. It has been reported that endoscopic ultrasonography (EUS) is essential for detecting tumors <10 mm with a favorable prognosis. Additionally, EUS‐guided fine‐needle aspiration biopsy is useful for confirming final histological diagnosis. For the diagnosis of stage 0 PC, local irregular stenosis of MPD should be an important initial abnormal sign detected by EUS or magnetic resonance cholangiopancreatography. Cytodiagnosis multiple times using pancreatic juice obtained by endoscopic nasopancreatic drainage should be essential for the final diagnosis. Recently, activities of regional networks between specialist doctors in medical centers and general practitioners for early diagnosis of PC have been reported in Japan. In the future, these activities may play an important role in the early diagnosis of PC.
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Affiliation(s)
- Keiji Hanada
- Department of Gastroenterology Onomichi General Hospital Hiroshima Japan
| | - Hironobu Amano
- Department of Surgery Onomichi General Hospital Hiroshima Japan
| | - Tomoyuki Abe
- Department of Surgery Onomichi General Hospital Hiroshima Japan
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30
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Bournet B, Vignolle-Vidoni A, Grand D, Roques C, Breibach F, Cros J, Muscari F, Carrère N, Selves J, Cordelier P, Buscail L. Endoscopic ultrasound-guided fine-needle aspiration plus KRAS and GNAS mutation in malignant intraductal papillary mucinous neoplasm of the pancreas. Endosc Int Open 2016; 4:E1228-E1235. [PMID: 27995180 PMCID: PMC5161125 DOI: 10.1055/s-0042-117216] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2016] [Accepted: 08/19/2016] [Indexed: 12/11/2022] Open
Abstract
Background:KRAS and GNAS mutations are common in intraductal papillary mucinous neoplasia of the pancreas (IPMN). The aims of this study were to assess the role of pre-therapeutic cytopathology combined with KRAS and GNAS mutation assays within cystic fluid sampled by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) to predict malignancy of IPMN. Patients and methods: We prospectively included 37 IPMN patients with clinical and/or imaging predictors of malignancy (men: 24; mean age: 69.5 years). Cytopathology (performed on cystic fluid and/or IPMN nodules), KRAS (Exon 2, codon 12) and GNAS (Exon 8, codon 201) mutations assays (using TaqMan® allelic discrimination) were performed on EUS-FNA material. The final diagnosis was obtained from IPMN resections (n = 18); surgical biopsies, EUS-FNA analyses, and follow-up (n = 19): 10 and 27 IPMN were benign and malignant, respectively. Results: Sensitivity, specificity, positive and negative predictive values, and accuracy of cytopathology alone to diagnose IPMN malignancy were 55 %, 100 %, 100 %, 45 %, and 66 %, respectively. When KRAS-mutation analysis was combined with cytopathology these values were 92 %, 50 %, 83 %, 71 %, and 81 %, respectively. GNAS assays did not improve the performances of cytopathology alone or those of cytopathology plus a KRAS assay. Conclusions: In patients with a likelihood of malignant IPMN at pre-therapeutic investigation, testing for KRAS mutations in cystic fluid sampling by EUS-FNA improved the results of cytopathology for the diagnosis of malignancy whereas GNAS mutation assay did not.
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Affiliation(s)
- Barbara Bournet
- Department of Gastroenterology and INSERM UMR 1037, CHU Toulouse Rangueil, University of Toulouse, Toulouse, France,INSERM UMR 1037, University Institute of Cancer of Toulouse, University of Toulouse, Toulouse, France
| | - Alix Vignolle-Vidoni
- INSERM UMR 1037, University Institute of Cancer of Toulouse, University of Toulouse, Toulouse, France
| | - David Grand
- Department of Pathology, University Institute of Cancer of Toulouse, University of Toulouse, Toulouse, France
| | - Céline Roques
- Department of Pathology, University Institute of Cancer of Toulouse, University of Toulouse, Toulouse, France
| | - Florence Breibach
- Department of Pathology, University Institute of Cancer of Toulouse, University of Toulouse, Toulouse, France
| | - Jérome Cros
- Department of Pathology, Beaujon Hospital, University of Paris Diderot, Clichy, France
| | - Fabrice Muscari
- Department of Digestive Surgery, CHU Toulouse Rangueil, University of Toulouse, Toulouse, France
| | - Nicolas Carrère
- INSERM UMR 1037, University Institute of Cancer of Toulouse, University of Toulouse, Toulouse, France,Department of Digestive Surgery, CHU Toulouse Purpan, University of Toulouse, Toulouse, France
| | - Janick Selves
- INSERM UMR 1037, University Institute of Cancer of Toulouse, University of Toulouse, Toulouse, France,Department of Pathology, University Institute of Cancer of Toulouse, University of Toulouse, Toulouse, France
| | - Pierre Cordelier
- INSERM UMR 1037, University Institute of Cancer of Toulouse, University of Toulouse, Toulouse, France
| | - Louis Buscail
- Department of Gastroenterology and INSERM UMR 1037, CHU Toulouse Rangueil, University of Toulouse, Toulouse, France,INSERM UMR 1037, University Institute of Cancer of Toulouse, University of Toulouse, Toulouse, France,Corresponding author Louis Buscail, MD, PhD Department of Gastroenterology and INSERM U1037CHU Rangueil1 avenue Jean PoulhèsTSA 5003231059 Toulouse Cedex 9France+33 5 61 32 30 55+33 5 61 32 22 29
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31
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The Clinical Indications for Limited Surgery of Intraductal Papillary Mucinous Neoplasms of the Pancreas. World J Surg 2016; 41:1358-1365. [DOI: 10.1007/s00268-016-3824-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
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32
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Hsiao CY, Yang CY, Wu JM, Kuo TC, Tien YW. Utility of the 2006 Sendai and 2012 Fukuoka guidelines for the management of intraductal papillary mucinous neoplasm of the pancreas: A single-center experience with 138 surgically treated patients. Medicine (Baltimore) 2016; 95:e4922. [PMID: 27661043 PMCID: PMC5044913 DOI: 10.1097/md.0000000000004922] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
This study aimed to evaluate the utility of the 2006 Sendai and 2012 Fukuoka guidelines for differentiating malignant intraductal papillary mucinous neoplasm (IPMN) of the pancreas from benign IPMN.Between January 2000 and March 2015, a total of 138 patients underwent surgery and had a pathologically confirmed pancreatic IPMN. Clinicopathological parameters were reviewed, and all patients were classified according to both the 2006 Sendai and 2012 Fukuoka guidelines. Univariate and multivariate analyses were used for identifying significant factors associated with malignancy in IPMN.There were 9 high-grade dysplasia (HGD) and 37 invasive cancers (ICs) in the 138 patients. The positive predictive value (PPV) and negative predictive value (NPV) of the Sendai and Fukuoka guidelines for HGD/IC was 35.1%, 43.3%, 100%, and 85.4%, respectively. Of the 36 patients with worrisome features using the Fukuoka guideline, 7 patients had HGD/IC in their IPMNs. According to the multivariate analysis, jaundice, tumors of ≥3 cm, presence of mural nodule on imaging, and aged <65 years were associated with HGD/IC in patients with IPMN.The Sendai guideline had a better NPV, but the Fukuoka guideline had a better PPV. We suggest that patients with worrisome features based on the Fukuoka guideline be aggressively managed.
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Affiliation(s)
| | | | | | | | - Yu-Wen Tien
- Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan, ROC
- Correspondence: Yu-Wen Tien, Department of Surgery, National Taiwan University Hospital, 7 Chung-Shan South Rd, Taipei 10002, Taiwan, ROC (e-mail: )
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33
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Intraductal papillary mucinous neoplasms of the pancreas with concurrent pancreatic and periampullary neoplasms. Eur J Surg Oncol 2016; 42:197-204. [DOI: 10.1016/j.ejso.2015.10.014] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2015] [Revised: 10/14/2015] [Accepted: 10/23/2015] [Indexed: 01/12/2023] Open
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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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Tanaka M. International consensus on the management of intraductal papillary mucinous neoplasm of the pancreas. ANNALS OF TRANSLATIONAL MEDICINE 2015; 3:286. [PMID: 26697446 DOI: 10.3978/j.issn.2305-5839.2015.11.09] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
International consensus guidelines for the management of intraductal papillary mucinous neoplasm (IPMN) of the pancreas revised in 2012 (Fukuoka consensus) seem to be accepted well worldwide. Division of various factors to predict malignant transformation into two categories, i.e., "high-risk stigmata" and "worrisome features", is also accepted as practically useful for stratifying the risk factors. Our current interest resides in the development of noninvasive and/or invasive pancreatic cancer in areas of the pancreas distinct from IPMN. Invasive pancreatic cancers derived from and concomitant with IPMN should be distinguished to clarify the incidence of each entity, although some more definitive method for differentiation has to be devised in some cases where histological distinction is obscure. IPMN is a clue to early detection of pancreatic cancer. The optimal surveillance protocol for IPMN on observation should be determined in consideration of both of these different pancreatic cancers.
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Affiliation(s)
- Masao Tanaka
- Shimonoseki City Hospital, 1-13-1 Koyo-cho, Shimonoseki 750-8520, Japan
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Sultana A, Jackson R, Tim G, Bostock E, Psarelli EE, Cox TF, Sutton R, Ghaneh P, Raraty MGT, Neoptolemos JP, Halloran CM. What Is the Best Way to Identify Malignant Transformation Within Pancreatic IPMN: A Systematic Review and Meta-Analyses. Clin Transl Gastroenterol 2015; 6:e130. [PMID: 26658837 PMCID: PMC4816095 DOI: 10.1038/ctg.2015.60] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2015] [Accepted: 11/03/2015] [Indexed: 12/17/2022] Open
Abstract
OBJECTIVES Pancreatic intraductal papillary mucinous neoplasias (IPMNs) represent 25% of all cystic neoplasms and are precursor lesions for pancreatic ductal adenocarcinoma. This study aims to identify the best imaging modality for detecting malignant transformation in IPMN, the sensitivity and specificity of risk features on imaging, and the usefulness of tumor markers in serum and cyst fluid to predict malignancy in IPMN. METHODS Databases were searched from November 2006 to March 2014. Pooled sensitivity and specificity of diagnostic techniques/imaging features of suspected malignancy in IPMN using a hierarchical summary receiver operator characteristic (HSROC) approach were performed. RESULTS A total of 467 eligible studies were identified, of which 51 studies met the inclusion criteria and 37 of these were incorporated into meta-analyses. The pooled sensitivity and specificity for risk features predictive of malignancy on computed tomography/magnetic resonance imaging were 0.809 and 0.762 respectively, and on positron emission tomography were 0.968 and 0.911. Mural nodule, cyst size, and main pancreatic duct dilation found on imaging had pooled sensitivity for prediction of malignancy of 0.690, 0.682, and 0.614, respectively, and specificity of 0.798, 0.574, and 0.687. Raised serum carbohydrate antigen 19-9 (CA19-9) levels yielded sensitivity of 0.380 and specificity of 0903. Combining parameters yielded a sensitivity of 0.743 and specificity of 0.906. CONCLUSIONS PET holds the most promise in identifying malignant transformation within an IPMN. Combining parameters increases sensitivity and specificity; the presence of mural nodule on imaging was the most sensitive whereas raised serum CA19-9 (>37 KU/l) was the most specific feature predictive of malignancy in IPMNs.
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Affiliation(s)
- Asma Sultana
- NIHR Pancreas Biomedical Research Unit, Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, University of Liverpool, Liverpool, UK
| | - Richard Jackson
- Medical Statistics, CRUK Liverpool Cancer Trials Unit, University of Liverpool, Liverpool, UK
| | - Gilbert Tim
- NIHR Pancreas Biomedical Research Unit, Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, University of Liverpool, Liverpool, UK
| | - Emma Bostock
- NIHR Pancreas Biomedical Research Unit, Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, University of Liverpool, Liverpool, UK
| | - Eftychia E Psarelli
- Medical Statistics, CRUK Liverpool Cancer Trials Unit, University of Liverpool, Liverpool, UK
| | - Trevor F Cox
- Medical Statistics, CRUK Liverpool Cancer Trials Unit, University of Liverpool, Liverpool, UK
| | - Robert Sutton
- NIHR Pancreas Biomedical Research Unit, Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, University of Liverpool, Liverpool, UK
| | - Paula Ghaneh
- NIHR Pancreas Biomedical Research Unit, Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, University of Liverpool, Liverpool, UK
| | - Michael G T Raraty
- NIHR Pancreas Biomedical Research Unit, Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, University of Liverpool, Liverpool, UK
| | - John P Neoptolemos
- NIHR Pancreas Biomedical Research Unit, Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, University of Liverpool, Liverpool, UK
| | - Christopher M Halloran
- NIHR Pancreas Biomedical Research Unit, Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, University of Liverpool, Liverpool, UK
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Tanaka M. Thirty years of experience with intraductal papillary mucinous neoplasm of the pancreas: from discovery to international consensus. Digestion 2015; 90:265-72. [PMID: 25591885 DOI: 10.1159/000370111] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is characterized by intraductal papillary proliferation of mucin-producing epithelial cells that exhibit various degrees of dysplasia. IPMN is classified as the main duct type (MD-IPMN) and the branch duct type (BD-IPMN) according to the location of involvement, and into four histological subtypes (gastric, intestinal, pancreatobiliary, and oncocytic) according to the histomorphological and immunohistochemical characteristics. Mucin core protein expression correlates with the biological behavior and prognosis of the tumor. DNA analysis has shown that IPMN is associated with a number of gene mutations, but the roles of many of these mutations require further investigation. Most patients with MD-IPMN undergo tumor resection. Patients with BD-IPMN who do not undergo resection may develop malignant change, and concomitant separate pancreatic cancer occurs in 2-10% of patients with IPMN. Patients with a strong family history may develop multiple BD-IPMNs as well as concomitant pancreatic cancer. Malignant changes are relatively easy to detect, especially by endoscopic ultrasonography (EUS), but the optimal surveillance protocol is currently unclear. KEY MESSAGES The 2012 guidelines for the management of IPMN recommend that patients with 'high-risk stigmata' (obstructive jaundice, enhanced solid component, and main pancreatic duct size ≥10 mm) should undergo resection. Patients with 'worrisome features' (cyst size ≥3 cm, thickened enhanced cyst walls, non-enhanced mural nodules, main pancreatic duct size 5-9 mm, abrupt change in main pancreatic duct caliber with distal pancreatic atrophy, lymphadenopathy, and clinical acute pancreatitis) should be evaluated by EUS. EUS is a more sensitive test than computed tomography or magnetic resonance imaging for the early detection of malignancy. CONCLUSIONS Most patients with MD-IPMN should undergo tumor resection. Patients with BD-IPMN who do not undergo resection should undergo careful surveillance including EUS for the early detection of malignant change and separate pancreatic cancer.
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Affiliation(s)
- Masao Tanaka
- Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
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Budde C, Beyer G, Kühn JP, Lerch MM, Mayerle J. The Clinical and Socio-Economic Relevance of Increased IPMN Detection Rates and Management Choices. VISZERALMEDIZIN 2015; 31:47-52. [PMID: 26286668 PMCID: PMC4433134 DOI: 10.1159/000375455] [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: 12/15/2022]
Abstract
Background Increased usage of computed tomography and magnetic resonance imaging has led to a large increase in identified pancreatic cysts of up to 25% in population-based studies. The clinical and economic relevance of identifying so many cystic lesions has not been established. Compared to other organs such as liver or kidney, dysontogenetic pancreatic cysts are rare. Pancreatic cysts comprise a variety of benign, premalignant or malignant lesions; however, precise diagnosis before resection has an accuracy of only 80%. The focus of recent research was the malignant potential of intraductal papillary mucinous neoplasms (IPMN) with the aim of establishing clinical pathways addressing risk of malignancy, age and comorbidity, treatment-related morbidity and mortality as well as cost-effectiveness of treatment and surveillance. The focus of this review is to analyze the clinical and socio-economic relevance as well as the cost-benefit relation for IPMNs. Methods For analysis, the following MESH terms were used to identify original articles, reviews, and guidelines in PubMed: (‘intraductal papillary mucinous neoplasm’ OR ‘pancreatic cysts’) and (incidence OR relevance OR socio-economic OR economic OR cost-effectiveness OR cost-benefit). The retrieved publications were reviewed with a focus on clinical and socio-economic relevance in relation to the increasing incidence of IPMN. Results Addressing the increasing prevalence of pancreatic cystic lesions, recent consensus guidelines suggested criteria for risk stratification according to ‘worrisome features’ and ‘high-risk stigmata’. Recent prospective cohort studies evaluated whether these can be applied in clinical practice. Evaluation of three different clinical scenarios with regard to costs and quality-adjusted life years suggested a better effectiveness of surveillance after initial risk stratification by endoscopic ultrasound-guided fine-needle aspiration with cyst fluid analysis compared with immediate resection or follow-up without further intervention. Of interest, the ‘immediate surgery’ strategy was lowest for cost-effectiveness. Conclusions The increasing incidence of identified pancreatic cysts requires an improved strategy for non-invasive risk stratification based on advanced imaging strategies. In light of a malignancy risk of 2% for branch-duct IPMN, the socio-economic necessity of a balance between surveillance and resection has to be agreed on.
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Affiliation(s)
- Christoph Budde
- Department of Medicine A, University Medicine, Ernst Moritz Arndt University Greifswald, Germany
| | - Georg Beyer
- Department of Medicine A, University Medicine, Ernst Moritz Arndt University Greifswald, Germany
| | - Jens-Peter Kühn
- Institute of Radiology, University Medicine, Ernst Moritz Arndt University Greifswald, Germany
| | - Markus M Lerch
- Department of Medicine A, University Medicine, Ernst Moritz Arndt University Greifswald, Germany
| | - Julia Mayerle
- Department of Medicine A, University Medicine, Ernst Moritz Arndt University Greifswald, Germany
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Akimoto Y, Nouso K, Kato H, Miyahara K, Dohi C, Morimoto Y, Kinugasa H, Tomoda T, Yamamoto N, Tsutsumi K, Kuwaki K, Onishi H, Ikeda F, Nakamura S, Shiraha H, Takaki A, Okada H, Amano M, Nishimura SI, Yamamoto K. Serum N-glycan profiles in patients with intraductal papillary mucinous neoplasms of the pancreas. Pancreatology 2015; 15:432-438. [PMID: 26052067 DOI: 10.1016/j.pan.2015.05.470] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2015] [Revised: 04/29/2015] [Accepted: 05/12/2015] [Indexed: 12/11/2022]
Abstract
BACKGROUND/OBJECTIVES Diagnosing the invasiveness of intraductal papillary mucinous neoplasms (IPMNs) is difficult, especially by blood test. Alterations in serum glycan profiles have been reported for several cancers, but changes in serum glycan profiles have not been investigated in patients with IPMNs. The objectives of this study were to determine the serum N-glycan profile and to investigate its clinical utility in patients with IPMNs. METHODS We measured serum N-glycan profiles in 79 patients with IPMNs, including 13 invasive IPMNs, by performing comprehensive glycome analysis and assessed the relationship between N-glycan changes and clinical parameters. RESULTS Seventy glycans were identified and their expression profiles were significantly different depending on the cyst size, the presence of an enhancing solid component, and the histological grade of the IPMN. Nine glycans were highly expressed in patients with invasive IPMNs. The glycan m/z 3195, which is a fucosylated tri-antennary glycan, had the highest diagnostic value for distinguishing invasive IPMNs from non-invasive IPMNs (area under the receiver operating characteristic curve = 0.803). Multivariate analyses revealed high levels of m/z 3195 [odds ratio (OR), 20.5; 95% confidence interval (CI) 2.60-486.4] and the presence of enhancing solid components (OR, 35.8; 95% CI, 5.39-409.6) were significant risk factors for invasive IPMNs. CONCLUSIONS We performed a comprehensive evaluation of the changes in serum N-glycan profiles in patients with IPMNs for the first time. We determined that increased expression of fucosylated complex-type glycans, especially m/z 3195, is a potential marker for invasive IPMNs.
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Affiliation(s)
- Yutaka Akimoto
- Department of Gastroenterology & Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
| | - Kazuhiro Nouso
- Department of Gastroenterology & Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
| | - Hironari Kato
- Department of Gastroenterology & Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
| | - Koji Miyahara
- Department of Gastroenterology & Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
| | - Chihiro Dohi
- Department of Gastroenterology & Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
| | - Yuki Morimoto
- Department of Gastroenterology & Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
| | - Hideaki Kinugasa
- Department of Gastroenterology & Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
| | - Takeshi Tomoda
- Department of Gastroenterology & Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
| | - Naoki Yamamoto
- Department of Gastroenterology & Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
| | - Koichiro Tsutsumi
- Department of Gastroenterology & Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
| | - Kenji Kuwaki
- Department of Gastroenterology & Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
| | - Hideki Onishi
- Department of Gastroenterology & Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
| | - Fusao Ikeda
- Department of Gastroenterology & Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
| | - Shinichiro Nakamura
- Department of Gastroenterology & Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
| | - Hidenori Shiraha
- Department of Gastroenterology & Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
| | - Akinobu Takaki
- Department of Gastroenterology & Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
| | - Hiroyuki Okada
- Department of Gastroenterology & Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan; Departments of Endoscopy, Okayama University Hospital, Okayama, Japan
| | - Maho Amano
- Field of Drug Discovery Research, Faculty of Advanced Life Science & Graduate School of Life Science, Hokkaido University, Sapporo, Hokkaido, Japan; Medicinal Chemistry Pharmaceuticals, Co., Ltd., Sapporo, Hokkaido, Japan
| | - Shin-Ichiro Nishimura
- Field of Drug Discovery Research, Faculty of Advanced Life Science & Graduate School of Life Science, Hokkaido University, Sapporo, Hokkaido, Japan; Medicinal Chemistry Pharmaceuticals, Co., Ltd., Sapporo, Hokkaido, Japan
| | - Kazuhide Yamamoto
- Department of Gastroenterology & Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
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Tanaka M. Current roles of endoscopy in the management of intraductal papillary mucinous neoplasm of the pancreas. Dig Endosc 2015; 27:450-457. [PMID: 25588761 PMCID: PMC4964938 DOI: 10.1111/den.12434] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2014] [Accepted: 01/09/2015] [Indexed: 02/06/2023]
Abstract
Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is characterized by intraductal papillary proliferation of mucin-producing epithelial cells that exhibit various degrees of dysplasia. IPMN is classified into four histological subtypes (gastric, intestinal, pancreatobiliary, and oncocytic) according to its histomorphological and immunohistochemical characteristics. Endoscopic retrograde cholangiopancreatography plays a crucial role in the evaluation of these features of IPMN. Endoscopic ultrasonography (EUS) has proven to be more sensitive than computed tomography or magnetic resonance imaging for early detection of malignancy. The present review addresses the current roles of endoscopy and related techniques in the management of IPMN. The particular focus is on diagnosing IPMN and malignancy within IPMN, detecting pancreatic cancer concomitant with IPMN, differentiating the epithelial subtypes of IPMN, determining the optimal strategy for the management of branch duct IPMN, and discussing innovative endoscopic technology related to IPMN. The disadvantages of endoscopic examinations of IPMN and different attitudes toward EUS-guided fine-needle aspiration for IPMN between Japan (negative) and other countries (active) are also discussed.
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Affiliation(s)
- Masao Tanaka
- Department of Surgery and OncologyGraduate School of Medical Sciences, Kyushu UniversityFukuokaJapan
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41
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Rezaee N, Khalifian S, Cameron JL, Pawlik TM, Hruban RH, Fishman EK, Makary MA, Lennon AM, Wolfgang CL, Weiss MJ. Smoking is not associated with severe dysplasia or invasive carcinoma in resected intraductal papillary mucinous neoplasms. J Gastrointest Surg 2015; 19:656-65. [PMID: 25477314 PMCID: PMC4363279 DOI: 10.1007/s11605-014-2714-y] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2014] [Accepted: 11/20/2014] [Indexed: 01/31/2023]
Abstract
INTRODUCTION Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas are precursor lesions that progress to invasive cancer through progressively worsening dysplasia. Although smoking is an established risk factor for pancreatic adenocarcinoma, potential associations with IPMN grade of dysplasia remain unclear. METHODS Pancreatic resections for IPMN from 1995 to 2013 were retrospectively reviewed. A total of 446 patients in which the smoking status was documented were identified. RESULTS Smoking history was positive in 47% of patients. Of smokers, 50% had branch-duct, 14% had main-duct, and 36% had mixed-type IPMN. Patients with main-duct IPMN were more commonly smokers (65%), compared to smoking history in 46% with mixed and 44% with branch-duct IPMN (p = 0.03). High-grade dysplasia occurred in 25% of smokers and 21% of nonsmokers (p = 0.32), and invasive carcinoma in 25% of smokers and 25% nonsmokers (p = 0.95). On multivariate analysis, duct size was independently associated with high-grade dysplasia (OR = 3.17, 95% CI = 1.79-5.64, p < 0.001). Presence of mural nodules (OR = 3.34, 95% CI = 1.82-6.12, p < 0.001), duct size (OR = 3.87, 95% CI = 2.21-6.75, p < 0.001), and symptoms (OR = 7.10, 95% CI = 3.80-13.08, p < 0.001), but not smoking history (OR = 1.10, 95% CI = 0.64-1.88, p = 0.73), were independent predictors of invasive carcinoma. Median overall survival was 70 months for smokers and 88 months for nonsmokers (p = 0.68). CONCLUSION Positive smoking history correlated with duct type classification but does not appear to be a risk factor for harboring high-grade dysplasia or invasive carcinoma in IPMNs.
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Affiliation(s)
- Neda Rezaee
- Departments of Surgery, Johns Hopkins University School of Medicine, 600 North Wolfe St, Halsted 608, Baltimore, MD 21287, USA
| | - Saami Khalifian
- Departments of Surgery, Johns Hopkins University School of Medicine, 600 North Wolfe St, Halsted 608, Baltimore, MD 21287, USA
| | - John L. Cameron
- Departments of Surgery, Johns Hopkins University School of Medicine, 600 North Wolfe St, Halsted 608, Baltimore, MD 21287, USA
| | - Timothy M. Pawlik
- Departments of Surgery, Johns Hopkins University School of Medicine, 600 North Wolfe St, Halsted 608, Baltimore, MD 21287, USA,Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Ralph H. Hruban
- Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA,Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Elliot K. Fishman
- Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Martin A. Makary
- Departments of Surgery, Johns Hopkins University School of Medicine, 600 North Wolfe St, Halsted 608, Baltimore, MD 21287, USA
| | - Anne Marie Lennon
- Departments of Surgery, Johns Hopkins University School of Medicine, 600 North Wolfe St, Halsted 608, Baltimore, MD 21287, USA,Department of Gastroenterology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Christopher L. Wolfgang
- Departments of Surgery, Johns Hopkins University School of Medicine, 600 North Wolfe St, Halsted 608, Baltimore, MD 21287, USA,Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA,Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Matthew J. Weiss
- Departments of Surgery, Johns Hopkins University School of Medicine, 600 North Wolfe St, Halsted 608, Baltimore, MD 21287, USA,Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
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Scheiman JM, Hwang JH, Moayyedi P. American gastroenterological association technical review on the diagnosis and management of asymptomatic neoplastic pancreatic cysts. Gastroenterology 2015; 148:824-48.e22. [PMID: 25805376 DOI: 10.1053/j.gastro.2015.01.014] [Citation(s) in RCA: 293] [Impact Index Per Article: 29.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Affiliation(s)
- James M Scheiman
- Department of Internal Medicine and Gastroenterology, University of Michigan Medical School, Ann Arbor, Michigan
| | - Joo Ha Hwang
- Division of Gastroenterology, Department of Medicine, University of Washington, Seattle, Washington
| | - Paul Moayyedi
- Division of Gastroenterology, Hamilton Health Sciences, Farncombe Family Digestive Health Research Institute, McMaster University Hamilton, Ontario, Canada
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Komatsu S, Ichikawa D, Miyamae M, Kawaguchi T, Morimura R, Hirajima S, Okajima W, Ohashi T, Imamura T, Konishi H, Shiozaki A, Ikoma H, Okamoto K, Taniguchi H, Otsuji E. Malignant potential in pancreatic neoplasm; new insights provided by circulating miR-223 in plasma. Expert Opin Biol Ther 2015; 15:773-85. [PMID: 25819175 DOI: 10.1517/14712598.2015.1029914] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
BACKGROUND Recent studies have identified that microRNAs are stably detectable in plasma/serum because of their binding to specific proteins or being packaged in secretory vesicles. METHODS We tested miR-223 as a candidate of novel plasma biomarker in pancreatic cancer (PCa) and intraductal papillary mucinous neoplasm (IPMN). RESULTS i) miR-223 expression was significantly higher in PCa tissues (p = 0.0069) than in normal tissues. ii) Plasma miR-223 levels were significantly higher in 71 PCa patients than 67 healthy volunteers (p < 0.0001). iii) Plasma miR-223 levels were significantly reduced in postoperative samples (p = 0.0297). iv) Plasma miR-223 levels tended to discriminate the malignant potential between benign IPMN and malignant IPMN (p = 0.0963), and the progressive extent of invasiveness between malignant IPMN and pancreatic invasive ductal carcinoma (PIDC) (p = 0.0004). Multivariate logistic regression analysis revealed that a low level of plasma miR-223 was an independent risk factor for PIDC (p = 0.0012, odds ratio 7.90 [95% CI: 2.06 - 41.2]). v) There was no significant correlation between plasma miR-223 levels and the number of any blood cell types in the peripheral blood. CONCLUSION Plasma miR-223 might be a clinically useful biomarker for screening PCa, and predicting malignant potential of IPMN and the invasiveness of PCa.
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Affiliation(s)
- Shuhei Komatsu
- Kyoto Prefectural University of Medicine, Division of Digestive Surgery, Department of Surgery , 465 Kajii-cho, Kawaramachihirokoji, Kamigyo-ku, Kyoto , Japan +81 75 251 5527 ; +81 75 251 5522 ;
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Jana T, Shroff J, Bhutani MS. Pancreatic cystic neoplasms: Review of current knowledge, diagnostic challenges, and management options. J Carcinog 2015; 14:3. [PMID: 25821410 PMCID: PMC4374202 DOI: 10.4103/1477-3163.153285] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2014] [Accepted: 02/01/2015] [Indexed: 12/12/2022] Open
Abstract
Pancreatic cystic lesions are being detected with increasing frequency, largely due to advances in cross-sectional imaging. The most common neoplasms include serous cystadenomas, mucinous cystic neoplasms, intraductal papillary mucinous neoplasms, solid pseudopapillary neoplasms, and cystic pancreatic endocrine neoplasms. Computed tomography (CT), magnetic resonance imaging (MRI), and endoscopic ultrasound (EUS) are currently used as imaging modalities. EUS-guided fine needle aspiration has proved to be a useful diagnostic tool, and enables an assessment of tumor markers, cytology, chemistries, and DNA analysis. Here, we review the current literature on pancreatic cystic neoplasms, including classification, diagnosis, treatment, and recommendations for surveillance. Data for this manuscript was acquired via searching the literature from inception to December 2014 on PubMed and Ovid MEDLINE.
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Affiliation(s)
- Tanima Jana
- Department of Internal Medicine, University of Texas Medical School at Houston, Houston, TX, USA
| | - Jennifer Shroff
- Department of Internal Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Texas Medical School at Houston, Houston, TX, USA
| | - Manoop S Bhutani
- Department of Gastroenterology, Hepatology and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
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Daudé M, Muscari F, Buscail C, Carrère N, Otal P, Selves J, Buscail L, Bournet B. Outcomes of nonresected main-duct intraductal papillary mucinous neoplasms of the pancreas. World J Gastroenterol 2015; 21:2658-2667. [PMID: 25759534 PMCID: PMC4351216 DOI: 10.3748/wjg.v21.i9.2658] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2014] [Revised: 10/12/2014] [Accepted: 12/08/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To compare characteristics and outcomes of resected and nonresected main-duct and mixed intraductal papillary mucinous neoplasms of the pancreas (IPMN).
METHODS: Over a 14-year period, 50 patients who did not undergo surgery for resectable main-duct or mixed IPMN, for reasons of precluding comorbidities, age and/or refusal, were compared with 74 patients who underwent resection to assess differences in rates of survival, recurrence/occurrence of malignancy, and prognostic factors. All study participants had dilatation of the main pancreatic duct by ≥ 5 mm, with or without dilatation of the branch ducts. Some of the nonsurgical patients showed evidence of mucus upon perendoscopic retrograde cholangiopancreatography or endoscopic ultrasound and/or after fine needle aspiration. For the surgical patients, pathologic analysis of resected specimens confirmed a diagnosis of IPMN with involvement of the main pancreatic duct or of both branch ducts as well as the main pancreatic duct. Clinical and biologic follow-ups were conducted for all patients at least annually, through hospitalization or consultation every six months during the first year of follow-up, together with abdominal imaging analysis (magnetic resonance cholangiopancreatography or computed tomography) and, if necessary, endoscopic ultrasound with or without fine needle aspiration.
RESULTS: The overall five-year survival rate of patients who underwent resection was significantly greater than that for the nonsurgical patients (74% vs 58%; P = 0.019). The parameters of age (< 70 years) and absence of a nodule were associated with better survival (P < 0.05); however, the parameters of main pancreatic duct diameter > 10 mm, branch duct diameter > 30 mm, or presence of extra pancreatic cancers did not significantly influence the prognosis. In the nonsurgical patients, pancreatic malignancy occurred in 36% of cases within a mean time of 33 mo (median: 29 mo; range: 8-141 mo). Comparison of the nonsurgical patients who experienced disease progression with those who did not progress showed no significant differences in age, sex, symptoms, subtype of IPMN, or follow-up period; only the size of the main pancreatic duct was significantly different between these two sub-groups, with the nonsurgical patients who experienced progression showing a greater diameter at the time of diagnosis (> 10 mm).
CONCLUSION: Patients unfit for surgery have a 36% greater risk of developing pancreatic malignancy of the main-duct or mixed IPMN within a median of 2.5 years.
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MESH Headings
- Adenocarcinoma, Mucinous/mortality
- Adenocarcinoma, Mucinous/pathology
- Adenocarcinoma, Mucinous/surgery
- Adenocarcinoma, Mucinous/therapy
- Adenocarcinoma, Papillary/mortality
- Adenocarcinoma, Papillary/pathology
- Adenocarcinoma, Papillary/surgery
- Adenocarcinoma, Papillary/therapy
- Adult
- Aged
- Aged, 80 and over
- Cholangiopancreatography, Endoscopic Retrograde
- Cholangiopancreatography, Magnetic Resonance
- Disease Progression
- Endoscopic Ultrasound-Guided Fine Needle Aspiration
- Endosonography
- Female
- Humans
- Kaplan-Meier Estimate
- Male
- Middle Aged
- Neoplasm Recurrence, Local
- Pancreatectomy/adverse effects
- Pancreatectomy/mortality
- Pancreatic Neoplasms/mortality
- Pancreatic Neoplasms/pathology
- Pancreatic Neoplasms/surgery
- Pancreatic Neoplasms/therapy
- Predictive Value of Tests
- Proportional Hazards Models
- Retrospective Studies
- Risk Factors
- Time Factors
- Tomography, X-Ray Computed
- Treatment Outcome
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Clinical significance of GNAS mutation in intraductal papillary mucinous neoplasm of the pancreas with concomitant pancreatic ductal adenocarcinoma. Pancreas 2015; 44:311-20. [PMID: 25479586 DOI: 10.1097/mpa.0000000000000258] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
OBJECTIVE The aims of this study were to investigate the GNAS mutational status in pancreatic intraductal papillary mucinous neoplasm (IPMN) with and without distinct pancreatic ductal adenocarcinoma (PDAC) and to evaluate the significance of GNAS analysis using duodenal fluid (DF) in patients with IPMN. METHODS The clinicopathologic features of 110 patients with IPMN including 16 with distinct PDAC were reviewed. The GNAS status in the IPMN tissue and 23 DF specimens was assessed by sensitive mutation scanning methods. RESULTS The GNAS mutation rate in IPMN with distinct PDAC was significantly lower than that in IPMN without PDAC (4/16, 25%, vs 61/94, 65%; P = 0.0047). By multivariate analysis, GNAS wild-type and gastric type IPMNs were significantly associated with distinct PDAC. Of 45 GNAS wild-type IPMNs, 10 (43%) of 23 gastric type IPMNs had distinct PDAC, whereas only 2 (9%) of 22 non-gastric type IPMNs had distinct PDAC (P = 0.017). The GNAS status in DF was consistent with that in tissue in 21 (91%) of 23 patients. CONCLUSIONS Distinct PDACs frequently develop in the pancreas with gastric type IPMN without GNAS mutations. Duodenal fluid DNA test would predict the GNAS status of IPMN, whereas the detection of the gastric subtype using noninvasive test remains to be determined.
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Koh YX, Zheng HL, Chok AY, Tan CS, Wyone W, Lim TKH, Tan DMY, Goh BKP. Systematic review and meta-analysis of the spectrum and outcomes of different histologic subtypes of noninvasive and invasive intraductal papillary mucinous neoplasms. Surgery 2015; 157:496-509. [PMID: 25656693 DOI: 10.1016/j.surg.2014.08.098] [Citation(s) in RCA: 59] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2014] [Revised: 08/05/2014] [Accepted: 08/26/2014] [Indexed: 12/23/2022]
Abstract
BACKGROUND Our aim was to review the available evidence to determine the clinical importance of the histologic subtypes of noninvasive and invasive intraductal papillary mucinous neoplasms (IPMNs) on disease characteristics and overall survival. METHODS We reviewed systematically 14 comparative studies that reported clinicopathologic characteristics and survival of 1,617 patients with IPMN (900 noninvasive and 717 invasive). RESULTS The pancreatobiliary subtype was associated with the greatest likelihood of tumor invasion (67.9%; odds ratio [OR], 2.87; 95% CI, 1.90-4.35), harboring an associated mural nodule (56.6%; OR, 2.92; 95% CI, 1.21-7.04), demonstrating tumor recurrence (46.3%; OR, 3.28; 95% CI, 1.41-7.66) and transformation to tubular adenocarcinoma (81.8%; OR, 92.96; 95% CI, 20.76-416.28) among all subtypes. The gastric subtype was associated with the least likelihood of tumor invasion (10.2%; OR, 0.18; 95% CI, 0.13-0.26), association with main duct IPMN (19.2%; OR, 0.12; 95% CI, 0.06-0.26), and tumor recurrence (9.4%; OR, 0.47; 95% CI, 0.26-0.83) among all subtypes. The intestinal subtype had the greatest likelihood of progressing to colloid carcinoma among all subtypes. Tubular adenocarcinoma was associated with an increased risk of vascular invasion (32.9%; OR, 4.86; 95% CI, 1.96-12.01), perineural invasion (54.5%; OR, 2.30; 95% CI, 1.22-4.34), nodal metastasis (52.4%; OR, 3.31; 95% CI, 1.79-6.14), and a positive margin status (17.3%; OR, 8.45; 95% CI, 1.52-46.83). Tubular adenocarcinoma (hazard ratio [HR], 1.90; 95% CI, 1.36-2.67) had a poorer 5-year overall survival compared with colloid carcinoma and was similar to the survival observed in pancreatic ductal adenocarcinoma (HR, 2.00; 95% CI, 1.59-2.52). CONCLUSION The prognosis of IPMN depends on its pathologic subtype. Subtype identification should be considered an essential component in future guidelines for the management of IPMN.
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Affiliation(s)
- Ye Xin Koh
- Department of Hepatopancreatobiliary and Transplantation Surgery, Singapore General Hospital, Singapore
| | - Hui Li Zheng
- Saw Swee Hock School of Public Health, National University of Singapore, Singapore
| | - Aik-Yong Chok
- Department of Hepatopancreatobiliary and Transplantation Surgery, Singapore General Hospital, Singapore
| | - Chuen Seng Tan
- Saw Swee Hock School of Public Health, National University of Singapore, Singapore
| | - Wyiki Wyone
- Department of Hepatopancreatobiliary and Transplantation Surgery, Singapore General Hospital, Singapore
| | - Tony K H Lim
- Department of Pathology, Singapore General Hospital, Singapore
| | - Damien M Y Tan
- Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore
| | - Brian K P Goh
- Department of Hepatopancreatobiliary and Transplantation Surgery, Singapore General Hospital, Singapore; Duke-NUS Graduate Medical School, Singapore.
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Haruki K, Wakiyama S, Futagawa Y, Shiba H, Misawa T, Yanaga K. A large mural nodule in branch duct intraductal papillary mucinous adenoma of the pancreas: a case report. Surg Case Rep 2015; 1:20. [PMID: 26943388 PMCID: PMC4747927 DOI: 10.1186/s40792-014-0009-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2014] [Accepted: 12/08/2014] [Indexed: 12/15/2022] Open
Abstract
Indications for resection of branch duct intraductal papillary mucinous neoplasms (IPMNs) remain controversial because of their low tendency to be malignant. Surgical resection should be recommended if any factors indicating malignancy are present. However, preoperative differentiation between benign and malignant tumors is very difficult, especially in cases of branch duct IPMNs. We herein report a case of branch duct intraductal papillary mucinous adenoma (IPMA) of the pancreas with a large mural nodule of 25 mm. A 74-year-old woman was admitted for examination and treatment for a cystic tumor in the head of the pancreas. Magnetic resonance cholangiopancreatography and computed tomography showed a cystic lesion, 50 mm in diameter, with an irregular mural nodule in the pancreatic head. Endoscopic ultrasonography demonstrated a multicystic tumor connected with the main pancreatic duct (MPD). The mural nodule had a diameter of 18 mm, and the MPD had a slight dilation of 6 mm. These findings suggested a high potential for malignancy. The patient underwent pancreaticoduodenectomy with lymph node dissection. The excised pancreas showed multiple cysts located in the branch pancreatic duct with a maximum diameter of 75 mm. The mural nodule had a maximum diameter of 25 mm. The tumor was diagnosed as an IPMA by pathological examination. After operation, the patient was discharged without any complications. Two years after resection, the patient remains in remission with no evidence of tumor recurrence.
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Affiliation(s)
- Koichiro Haruki
- Department of Surgery, The Jikei University School of Medicine, 3-25-8, Nishi-Shinbashi, Minato-ku, Tokyo, 105-8461, Japan.
| | - Shigeki Wakiyama
- Department of Surgery, The Jikei University School of Medicine, 3-25-8, Nishi-Shinbashi, Minato-ku, Tokyo, 105-8461, Japan.
| | - Yasuro Futagawa
- Department of Surgery, The Jikei University School of Medicine, 3-25-8, Nishi-Shinbashi, Minato-ku, Tokyo, 105-8461, Japan.
| | - Hiroaki Shiba
- Department of Surgery, The Jikei University School of Medicine, 3-25-8, Nishi-Shinbashi, Minato-ku, Tokyo, 105-8461, Japan.
| | - Takeyuki Misawa
- Department of Surgery, The Jikei University School of Medicine, 3-25-8, Nishi-Shinbashi, Minato-ku, Tokyo, 105-8461, Japan.
| | - Katsuhiko Yanaga
- Department of Surgery, The Jikei University School of Medicine, 3-25-8, Nishi-Shinbashi, Minato-ku, Tokyo, 105-8461, Japan.
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Current recommendations for surveillance and surgery of intraductal papillary mucinous neoplasms may overlook some patients with cancer. J Gastrointest Surg 2015; 19:258-65. [PMID: 25373706 PMCID: PMC4305480 DOI: 10.1007/s11605-014-2693-z] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2014] [Accepted: 10/26/2014] [Indexed: 01/31/2023]
Abstract
BACKGROUND The 2012 Sendai Criteria recommend that patients with 3 cm or larger branch duct intraductal papillary mucinous neoplasms (BD-IPMN) without any additional "worrisome features" or "high-risk stigmata" may undergo close observation. Furthermore, endoscopic ultrasound (EUS) is not recommended for BD-IPMN <2 cm. These changes have generated concern among physicians treating patients with pancreatic diseases. The purposes of this study were to (i) apply the new Sendai guidelines to our institution's surgically resected BD-IPMN and (ii) reevaluate cyst size cutoffs in identifying patients with lesions harboring high-grade dysplasia or invasive cancer. METHODS We retrospectively reviewed 150 patients at a university medical center with preoperatively diagnosed and pathologically confirmed IPMNs. Sixty-six patients had BD-IPMN. Pathologic grade was dichotomized into low-grade (low or intermediate grade dysplasia) or high-grade/invasive (high-grade dysplasia or invasive cancers). Fisher's exact test, chi-square test, student's t test, linear regression, and receiver operating characteristic (ROC) analyses were performed. RESULTS The median BD-IPMN size on imaging was 2.4 cm (interquartile range 1.5-3.0). Fifty-one (77 %) low-grade and 15 (23 %) high-grade/invasive BD-IPMN were identified. ROC analysis demonstrated that cyst size on preoperative imaging is a reasonable predictor of grade with an area under the curve of 0.691. Two-thirds of high-grade/invasive BD-IPMN were <3 cm (n = 10). Compared to a cutoff of 3, 2 cm was associated with higher sensitivity (73.3 vs. 33.3 %) and negative predictive value (83.3 vs. 80 %, NPV) for high-grade/invasive BD-IPMN. Mural nodules on endoscopic ultrasound (EUS) or atypical cells on endoscopic ultrasound-fine needle aspiration (EUS-FNA) were identified in all cysts <2 and only 50 % of those <3 cm. Forty percent of cysts >3 cm were removed based on size alone. DISCUSSION/CONCLUSIONS Our results suggest that "larger" size on noninvasive imaging can indicate high-grade/invasive cysts, and EUS-FNA may help identify "smaller" cysts with high-grade/invasive pathology.
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Predictors of early stages of histological progression of branch duct IPMN. Langenbecks Arch Surg 2014; 400:49-56. [DOI: 10.1007/s00423-014-1259-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2014] [Accepted: 11/17/2014] [Indexed: 01/20/2023]
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