|
1
|
Ahmed TM, Kawamoto S, Lopez-Ramirez F, Yasrab M, Hruban RH, Fishman EK, Chu LC. Early detection of pancreatic cancer in the era of precision medicine. Abdom Radiol (NY) 2024; 49:3559-3573. [PMID: 38761272 DOI: 10.1007/s00261-024-04358-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2024] [Revised: 04/23/2024] [Accepted: 04/23/2024] [Indexed: 05/20/2024]
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer-related mortality and it is often diagnosed at advanced stages due to non-specific clinical presentation. Disease detection at localized disease stage followed by surgical resection remains the only potentially curative treatment. In this era of precision medicine, a multifaceted approach to early detection of PDAC includes targeted screening in high-risk populations, serum biomarkers and "liquid biopsies", and artificial intelligence augmented tumor detection from radiologic examinations. In this review, we will review these emerging techniques in the early detection of PDAC.
Collapse
Affiliation(s)
- Taha M Ahmed
- The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Hospital, Baltimore, MD, USA
| | - Satomi Kawamoto
- The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Hospital, Baltimore, MD, USA
| | - Felipe Lopez-Ramirez
- The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Hospital, Baltimore, MD, USA
| | - Mohammad Yasrab
- The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Hospital, Baltimore, MD, USA
| | - Ralph H Hruban
- Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Elliot K Fishman
- The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Hospital, Baltimore, MD, USA
| | - Linda C Chu
- The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Hospital, Baltimore, MD, USA.
| |
Collapse
|
|
2
|
Kane WJ, Haden KR, Martin EN, Shami VM, Wang AY, Strand DS, Adair SJ, Nagdas S, Tsung A, Zaydfudim VM, Adams RB, Bauer TW. Survival benefit associated with screening of patients at elevated risk for pancreatic cancer. J Surg Oncol 2024; 130:485-492. [PMID: 39016067 DOI: 10.1002/jso.27784] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2024] [Accepted: 06/30/2024] [Indexed: 07/18/2024]
Abstract
BACKGROUND & OBJECTIVES: Screening for pancreatic cancer is recommended for individuals with a strong family history, certain genetic syndromes, or a neoplastic cyst of the pancreas. However, limited data supports a survival benefit attributable to screening these higher-risk individuals. METHODS All patients enrolled in screening at a High-Risk Pancreatic Cancer Clinic (HRC) from July 2013 to June 2020 were identified from a prospectively maintained institutional database and compared to patients evaluated at a Surgical Oncology Clinic (SOC) at the same institution during the same period. Clinical outcomes of patients selected for surgical resection, particularly clinicopathologic stage and overall survival, were compared. RESULTS Among 826 HRC patients followed for a median (IQR) of 2.3 (0.8-4.2) years, 128 were selected for surgical resection and compared to 402 SOC patients selected for resection. Overall survival was significantly longer among HRC patients (median survival: not reached vs. 2.6 years, p < 0.001). Among 31 HRC and 217 SOC patients with a diagnosis of pancreatic ductal adenocarcinoma (PDAC), the majority of HRC patients were diagnosed with stage 0 disease (carcinoma in situ), while the majority of SOC patients were diagnosed with stage II disease (p < 0.001). Overall survival after resection of invasive PDAC was also significantly longer among HRC patients compared to SOC patients (median survival 5.5 vs. 1.6 years, p = 0.002). CONCLUSION Patients at increased risk for PDAC and followed with guideline-based screening exhibited downstaging of disease and improved survival from PDAC in comparison to patients who were not screened.
Collapse
Affiliation(s)
- William J Kane
- Department of Surgery, University of Virginia, Charlottesville, Virginia, USA
| | - Kathleen R Haden
- Department of Surgery, University of Virginia, Charlottesville, Virginia, USA
| | - Elizabeth N Martin
- Department of Surgery, University of Virginia, Charlottesville, Virginia, USA
| | - Vanessa M Shami
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Virginia, Charlottesville, Virginia, USA
| | - Andrew Y Wang
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Virginia, Charlottesville, Virginia, USA
| | - Daniel S Strand
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Virginia, Charlottesville, Virginia, USA
| | - Sara J Adair
- Department of Surgery, University of Virginia, Charlottesville, Virginia, USA
| | - Sarbajeet Nagdas
- School of Medicine, University of Virginia, Charlottesville, University of Virginia, USA
| | - Allan Tsung
- Department of Surgery, University of Virginia, Charlottesville, Virginia, USA
| | - Victor M Zaydfudim
- Department of Surgery, University of Virginia, Charlottesville, Virginia, USA
| | - Reid B Adams
- Department of Surgery, University of Virginia, Charlottesville, Virginia, USA
| | - Todd W Bauer
- Department of Surgery, University of Virginia, Charlottesville, Virginia, USA
| |
Collapse
|
|
3
|
Bogdanski AM, van Hooft JE, Boekestijn B, Bonsing BA, Wasser MNJM, Klatte DCF, van Leerdam ME. Aspects and outcomes of surveillance for individuals at high-risk of pancreatic cancer. Fam Cancer 2024; 23:323-339. [PMID: 38619782 PMCID: PMC11255004 DOI: 10.1007/s10689-024-00368-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2024] [Accepted: 02/24/2024] [Indexed: 04/16/2024]
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer-related deaths and is associated with a poor prognosis. The majority of these cancers are detected at a late stage, contributing to the bad prognosis. This underscores the need for novel, enhanced early detection strategies to improve the outcomes. While population-based screening is not recommended due to the relatively low incidence of PDAC, surveillance is recommended for individuals at high risk for PDAC due to their increased incidence of the disease. However, the outcomes of pancreatic cancer surveillance in high-risk individuals are not sorted out yet. In this review, we will address the identification of individuals at high risk for PDAC, discuss the objectives and targets of surveillance, outline how surveillance programs are organized, summarize the outcomes of high-risk individuals undergoing pancreatic cancer surveillance, and conclude with a future perspective on pancreatic cancer surveillance and novel developments.
Collapse
Affiliation(s)
- Aleksander M Bogdanski
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands.
| | - Jeanin E van Hooft
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands
| | - Bas Boekestijn
- Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands
| | - Bert A Bonsing
- Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
| | - Martin N J M Wasser
- Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands
| | - Derk C F Klatte
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands
| | - Monique E van Leerdam
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands
- Department of Gastrointestinal Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands
| |
Collapse
|
|
4
|
Overbeek KA, Cahen DL, Bruno MJ. The role of endoscopic ultrasound in the detection of pancreatic lesions in high-risk individuals. Fam Cancer 2024; 23:279-293. [PMID: 38573399 PMCID: PMC11255057 DOI: 10.1007/s10689-024-00380-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2023] [Accepted: 03/17/2024] [Indexed: 04/05/2024]
Abstract
Individuals at high risk of developing pancreatic ductal adenocarcinoma are eligible for surveillance within research programs. These programs employ periodic imaging in the form of magnetic resonance imaging/magnetic resonance cholangiopancreatography or endoscopic ultrasound for the detection of early cancer or high-grade precursor lesions. This narrative review discusses the role of endoscopic ultrasound within these surveillance programs. It details its overall strengths and limitations, yield, burden on patients, and how it compares to magnetic resonance imaging. Finally, recommendations are given when and how to incorporate endoscopic ultrasound in the surveillance of high-risk individuals.
Collapse
Affiliation(s)
- Kasper A Overbeek
- Erasmus MC Cancer Institute, Department of Gastroenterology & Hepatology, University Medical Center Rotterdam, Rotterdam, The Netherlands.
| | - Djuna L Cahen
- Erasmus MC Cancer Institute, Department of Gastroenterology & Hepatology, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Marco J Bruno
- Erasmus MC Cancer Institute, Department of Gastroenterology & Hepatology, University Medical Center Rotterdam, Rotterdam, The Netherlands
| |
Collapse
|
|
5
|
Silva-Santisteban A, Hernandez Woodbine MJ, Noriega MA, Rabinowitz LG, Grimshaw A, Farrell JJ, Chhoda A, Sawhney MS. Disparities in race, ethnicity, sex, and age inclusion in pancreatic cancer screening studies: a systematic review and meta-analysis. Gastrointest Endosc 2024; 100:1-16.e20. [PMID: 38432492 DOI: 10.1016/j.gie.2024.02.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2023] [Revised: 02/12/2024] [Accepted: 02/26/2024] [Indexed: 03/05/2024]
Abstract
BACKGROUND AND AIMS Substantial differences exist in pancreatic cancer outcomes across ethnoracial stratifications. We sought to assess racial, ethnic, sex, and age reporting and inclusion of participants in pancreatic cancer screening studies. METHODS A systematic search of Cochrane Library, Ovid Embase, Google Scholar, Ovid MEDLINE, PubMed, Scopus, and Web of Science Core Collection from inception to 2022 was conducted. Original studies on pancreatic cancer screening were identified and assessed for reporting and inclusion on race, ethnicity, sex, and age. The pooled proportions of study participants for these characteristics were calculated and compared with population-based benchmarks. RESULTS Among 27 eligible pancreatic cancer screening studies, 26 reported data on either sex, race, or ethnicity, with a total of 5273 participants. Information on participant sex was reported by 26, race by 12, and ethnicity by 8 studies. Participants in these studies were almost all white (pooled proportion, 93.1%; 95% confidence interval [CI], 89.7-96.4) and non-Latino (pooled proportion, 97.4%; 95% CI, 94.0-100), and these groups were over-represented when compared with the general population. Female participants were well represented, with a pooled proportion of 63.2% (95% CI, 59.9-66.6). When reported, mean or median participant age was <60 years. Meta-regression revealed higher proportions of female participants in studies from the United States (P = .002). No association between increasing participation of racial or ethnic under-represented populations and study quality, ascending year of publication, or source of study funding was noted. CONCLUSIONS Substantial disparities in race, ethnicity, sex, and age reporting and inclusion in pancreatic cancer studies were noted, even among high-quality and publicly funded studies.
Collapse
Affiliation(s)
- Andy Silva-Santisteban
- Division of Gastroenterology & Hepatology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA
| | - Maria Jose Hernandez Woodbine
- Division of Gastroenterology & Hepatology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA
| | - Marco Antonio Noriega
- Division of Gastroenterology & Hepatology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA
| | - Loren G Rabinowitz
- Division of Gastroenterology & Hepatology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA
| | - Alyssa Grimshaw
- Cushing/Whitney Medical Library, Yale University, New Haven, Connecticut, USA
| | - James J Farrell
- Division of Gastroenterology, Department of Medicine, Yale School of Medicine, New Haven, Connecticut, USA
| | - Ankit Chhoda
- Division of Gastroenterology & Hepatology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA
| | - Mandeep S Sawhney
- Division of Gastroenterology & Hepatology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA
| |
Collapse
|
|
6
|
Peters MLB, Eckel A, Seguin CL, Davidi B, Howard DH, Knudsen AB, Pandharipande PV. Cost-Effectiveness Analysis of Screening for Pancreatic Cancer Among High-Risk Populations. JCO Oncol Pract 2024; 20:278-290. [PMID: 38086003 PMCID: PMC10911581 DOI: 10.1200/op.23.00495] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2023] [Revised: 10/05/2023] [Accepted: 10/30/2023] [Indexed: 12/19/2023] Open
Abstract
PURPOSE We evaluated the potential cost-effectiveness of combined magnetic resonance imaging (MRI) and endoscopic ultrasound (EUS) screening for pancreatic ductal adenocarcinoma (PDAC) among populations at high risk for the disease. METHODS We used a microsimulation model of the natural history of PDAC to estimate the lifetime health benefits, costs, and cost-effectiveness of PDAC screening among populations with specific genetic risk factors for PDAC, including BRCA1 and BRCA2, PALB2, ATM, Lynch syndrome, TP53, CDKN2A, and STK11. For each high-risk population, we simulated 29 screening strategies, defined by starting age and frequency. Screening included MRI with follow-up EUS in a subset of patients. Costs of tests were based on Medicare reimbursement for MRI, EUS, fine-needle aspiration biopsy, and pancreatectomy. Cancer-related cost by stage of disease and phase of treatment was based on the literature. For each high-risk population, we performed an incremental cost-effectiveness analysis, assuming a willingness-to-pay (WTP) threshold of $100,000 US dollars (USD) per quality-adjusted life year (QALY) gained. RESULTS For men with relative risk (RR) 12.33 (CDKN2A) and RR 28 (STK11), annual screening was cost-effective, starting at age 55 and 40 years, respectively. For women, screening was only cost-effective for those with RR 28 (STK11), with annual screening starting at age 45 years. CONCLUSION Combined MRI/EUS screening may be a cost-effective approach for the highest-risk populations (among mutations considered, those with RR >12). However, for those with moderate risk (RR, 5-12), screening would only be cost-effective at higher WTP thresholds (eg, $200K USD/QALY) or with once-only screening.
Collapse
Affiliation(s)
- Mary Linton B. Peters
- Division of Medical Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA
- Institute for Technology Assessment, Massachusetts General Hospital, Boston, MA
| | - Andrew Eckel
- Institute for Technology Assessment, Massachusetts General Hospital, Boston, MA
| | - Claudia L. Seguin
- Department of Radiology, The Ohio State University College of Medicine, Columbus, OH
| | - Barak Davidi
- Institute for Technology Assessment, Massachusetts General Hospital, Boston, MA
| | - David H. Howard
- Department of Health Policy and Management, Rollins School of Public Health, Emory University, Atlanta, GA
| | - Amy B. Knudsen
- Institute for Technology Assessment, Massachusetts General Hospital, Boston, MA
- Department of Radiology, Massachusetts General Hospital, Boston, MA
| | - Pari V. Pandharipande
- Department of Radiology, The Ohio State University College of Medicine, Columbus, OH
| |
Collapse
|
|
7
|
Koltai T. Earlier Diagnosis of Pancreatic Cancer: Is It Possible? Cancers (Basel) 2023; 15:4430. [PMID: 37760400 PMCID: PMC10526520 DOI: 10.3390/cancers15184430] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2023] [Revised: 07/31/2023] [Accepted: 08/06/2023] [Indexed: 09/29/2023] Open
Abstract
Pancreatic ductal adenocarcinoma has a very high mortality rate which has been only minimally improved in the last 30 years. This high mortality is closely related to late diagnosis, which is usually made when the tumor is large and has extensively infiltrated neighboring tissues or distant metastases are already present. This is a paradoxical situation for a tumor that requires nearly 15 years to develop since the first founding mutation. Response to chemotherapy under such late circumstances is poor, resistance is frequent, and prolongation of survival is almost negligible. Early surgery has been, and still is, the only approach with a slightly better outcome. Unfortunately, the relapse percentage after surgery is still very high. In fact, early surgery clearly requires early diagnosis. Despite all the advances in diagnostic methods, the available tools for improving these results are scarce. Serum tumor markers permit a late diagnosis, but their contribution to an improved therapeutic result is very limited. On the other hand, effective screening methods for high-risk populations have not been fully developed as yet. This paper discusses the difficulties of early diagnosis, evaluates whether the available diagnostic tools are adequate, and proposes some simple and not-so-simple measures to improve it.
Collapse
Affiliation(s)
- Tomas Koltai
- Hospital del Centro Gallego de Buenos Aires, Buenos Aires C1094, Argentina
| |
Collapse
|
|
8
|
Maio F, Pasqualino V, Bertana L, Venturini S, Cantoni V, Fusaro M, Morana G. Pancreatic cancer detection with a non-contrast MR protocol: is it reliable? LA RADIOLOGIA MEDICA 2023; 128:1035-1046. [PMID: 37515631 PMCID: PMC10474201 DOI: 10.1007/s11547-023-01680-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/04/2023] [Accepted: 07/05/2023] [Indexed: 07/31/2023]
Abstract
PURPOSE The pancreatic cancer (PC) is the 4th leading cancer-related death, becoming the second one by 2030, with a 5 year survival rate of 8%. Considering its increased incidence in high-risk categories compared to the general population, we aimed to validate a non-contrast MR protocol, to detect PC in its earliest phase, which could be suitable as a screening tool in high-risk patients. MATERIALS AND METHODS In this retrospective study, we selected 200 patients (> 40 years) from our radiological database, which performed upper abdominal MRI between 2012 and 2017. 100 were negative for pancreatic lesions and 100 positive for pancreatic lesion (< 30 mm). The latter group included: 40 PDAC (pancreatic adenocarcinoma), 42 BD-IPMN (Branch Duct- Intraductal Papillary Mucinous Neoplasm), 10 PNET(pancreatic neuroendocrine tumor), 4 SCN(serous cystic neoplasm), 3 IPS(intrapancreatic spleen), 1 MCN(mucinous cystic neoplasm). Three readers (R1, R2 and R3) with a high, medium and low experience, respectively, analysed, first, the non-contrast MR sequences (single-shot T2w breath-hold, GE T1w FS, DWI and 2D/3D MRCP), and then the standard MR protocol, independently, randomly and anonymously. Readers identified or excluded the presence of pancreatic lesion, in both reading sessions. These results were compared with the histopathological diagnosis, and then divided into 3 different classes of lesions: all lesions, pancreatic adenocarcinoma and solid lesion. Mcnemar's test was used to compare the results. The inter-observer agreement was determined according to the kappa statistic in both protocols, and then the inter-protocol agreement was calculated. RESULTS The non-contrast MR protocol has reached statistical parameters values ranging between 83% in SE (sensitivity) by R3 and 99% in NPV (negative predictive value) by R1. The standard MR protocol has reported slight increasing statistical parameters compared to those of the proposed one. However, there are not significant statistical differences between the both protocols. The proposed non-contrast MR protocol has reported the highest NPVs in the PDAC group detection (R1: 99%, R2: 99%, R3: 98%). In all groups of lesions, the agreement between the two protocols was excellent for each Reader ranging from 96 to 98%. CONCLUSION The proposed non-contrast MR protocol showed high PC detection values and a time execution ≤ 20 min. Therefore, it can be proposed as a screening tool in high-risk patients.
Collapse
Affiliation(s)
- Francesca Maio
- Department of Advanced Biomedical Sciences, Federico II University, Via Pansini 5, 80131 Naples, Italy
- National Cancer Institute IRCCS “Fondazione G. Pascale” Radiology Department, Via Semmola 52, 80131 Naples, Italy
| | - Vincenzo Pasqualino
- Department of Radiology, Padua University, Via 8 Febbraio 1848, 2, 35122 Padua, Italy
| | - Luca Bertana
- Department of Radiology, General Hospital Ca’ Foncello, Piazzale dell’ Ospedale 1, 31100 Treviso, Italy
| | - Silvia Venturini
- Department of Radiology, General Hospital Ca’ Foncello, Piazzale dell’ Ospedale 1, 31100 Treviso, Italy
| | - Valeria Cantoni
- Department of Advanced Biomedical Sciences, Federico II University, Via Pansini 5, 80131 Naples, Italy
| | - Michele Fusaro
- Department of Radiology, General Hospital Ca’ Foncello, Piazzale dell’ Ospedale 1, 31100 Treviso, Italy
| | - Giovanni Morana
- Department of Radiology, General Hospital Ca’ Foncello, Piazzale dell’ Ospedale 1, 31100 Treviso, Italy
| |
Collapse
|
|
9
|
Haimi I, Sanoba S, Everett J, Simeone DM. Are All Cysts Created Equal?: Pancreatic Cystic Neoplasms in Patients with Familial or Genetic Risk Factors for Pancreatic Cancer. Gastrointest Endosc Clin N Am 2023; 33:547-557. [PMID: 37245935 DOI: 10.1016/j.giec.2023.03.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/30/2023]
Abstract
Pancreatic cystic lesions (PCLs) have become more prevalent over time, particularly in asymptomatic individuals. Current screening guidelines for incidental PCLs offer a unified approach to surveillance and management, predicated on "worrisome features." Although PCLs are common in the general population, their prevalence may be higher in high-risk individuals (HRI, unaffected patients with specific familial and/or genetic risk factors). As more PCLs are diagnosed and more HRI identified, it is important to promote research that bridges data gaps and introduces nuance to risk assessment tools, ensuring tailoring of guidelines to the needs of HRI with varying pancreatic cancer risk factors.
Collapse
Affiliation(s)
- Ido Haimi
- Department of Surgery, NYU Langone Health, 240 East 38th Street, 20th Floor, New York, NY 10016, USA
| | - Shenin Sanoba
- Perlmutter Cancer Center, NYU Langone Health, 240 East 38th Street, 20th Floor, New York, NY 10016, USA
| | - Jessica Everett
- Perlmutter Cancer Center, NYU Langone Health, 240 East 38th Street, 20th Floor, New York, NY 10016, USA
| | - Diane M Simeone
- Department of Surgery, NYU Langone Health, 240 East 38th Street, 20th Floor, New York, NY 10016, USA; Perlmutter Cancer Center, NYU Langone Health, 240 East 38th Street, 20th Floor, New York, NY 10016, USA; Pancreatic Cancer Center, 240 East 38th Street, 20th Floor, New York, NY 10016, USA.
| |
Collapse
|
|
10
|
Tavano F, Gioffreda D, Fontana A, Palmieri O, Gentile A, Latiano T, Latiano A, Latiano TP, Scaramuzzi M, Maiello E, Bazzocchi F, Perri F. Evaluation of inherited germline mutations in cancer susceptibility genes among pancreatic cancer patients: a single-center study. Mol Med 2023; 29:14. [PMID: 36717774 PMCID: PMC9885574 DOI: 10.1186/s10020-023-00600-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2022] [Accepted: 01/04/2023] [Indexed: 01/31/2023] Open
Abstract
BACKGROUND Germline mutations in cancer susceptibility genes were identified in pancreatic cancer (PanC) patients with a sporadic disease and in those unselected for family cancer history. METHODS With the aim to determine the prevalence of germline predisposition genes mutations in PanC, and to evaluate whether they were associated with the presence of PanC, we profiled a custom AmpliSeq panel of 27 cancer susceptibility genes in 47 PanC patients and 51 control subjects by using the Ion Torrent PGM system. RESULTS Multigene panel testing identified a total of 31 variants in 27 PanC (57.4%), including variants with pathogenic/likely pathogenic effect, those of uncertain significance, and variants whose clinical significance remains currently undefined. Five patients carried more than one variant in the same gene or in different genes. Eight patients (17.0%) had at least one pathogenic/likely pathogenic variant in four main genes: CFTR (10.6%), BRCA2 (8.5%), ATM and CHEK2 (2.1%). Pathogenic/likely pathogenic mutation were identified in patients with positive PanC family history (20%) or in patients without first-degree relatives affected by PanC (13.6%). All the BRCA2 mutation carriers were unselected PanC patients. The presence of mutations in BRCA2 was significantly associated with an increased occurrence of PanC and with positive family history for endometrial cancer (p = 0.018). CONCLUSIONS This study confirmed the potential remarkable contribution of BRCA2 in assessing the presence of PanC. Overall our findings supported the recommendation of offering the germline testing to all the PanC patients with the intent to reduce the number of underdiagnosed carriers of mutations in predisposition genes, and not to preclude their relatives from the opportunity to benefit from surveillance programs.
Collapse
Affiliation(s)
- Francesca Tavano
- grid.413503.00000 0004 1757 9135Division of Gastroenterology, Fondazione “Casa Sollievo della Sofferenza” IRCCS Hospital, Viale Cappuccini 1, FG 71013 San Giovanni Rotondo, Italy
| | - Domenica Gioffreda
- grid.413503.00000 0004 1757 9135Division of Gastroenterology, Fondazione “Casa Sollievo della Sofferenza” IRCCS Hospital, Viale Cappuccini 1, FG 71013 San Giovanni Rotondo, Italy
| | - Andrea Fontana
- grid.413503.00000 0004 1757 9135Unit of Biostatistics, Fondazione “Casa Sollievo della Sofferenza” IRCCS Hospital, Viale Cappuccini 1, FG 71013 San Giovanni Rotondo, Italy
| | - Orazio Palmieri
- grid.413503.00000 0004 1757 9135Division of Gastroenterology, Fondazione “Casa Sollievo della Sofferenza” IRCCS Hospital, Viale Cappuccini 1, FG 71013 San Giovanni Rotondo, Italy
| | - Annamaria Gentile
- grid.413503.00000 0004 1757 9135Division of Gastroenterology, Fondazione “Casa Sollievo della Sofferenza” IRCCS Hospital, Viale Cappuccini 1, FG 71013 San Giovanni Rotondo, Italy
| | - Tiziana Latiano
- grid.413503.00000 0004 1757 9135Division of Gastroenterology, Fondazione “Casa Sollievo della Sofferenza” IRCCS Hospital, Viale Cappuccini 1, FG 71013 San Giovanni Rotondo, Italy
| | - Anna Latiano
- grid.413503.00000 0004 1757 9135Division of Gastroenterology, Fondazione “Casa Sollievo della Sofferenza” IRCCS Hospital, Viale Cappuccini 1, FG 71013 San Giovanni Rotondo, Italy
| | - Tiziana Pia Latiano
- grid.413503.00000 0004 1757 9135Department of Oncology, Fondazione “Casa Sollievo della Sofferenza” IRCCS Hospital, Viale Cappuccini 1, FG 71013 San Giovanni Rotondo, Italy
| | - Matteo Scaramuzzi
- grid.413503.00000 0004 1757 9135Department of Surgery, Fondazione “Casa Sollievo della Sofferenza” IRCCS Hospital, Viale Cappuccini 1, FG 71013 San Giovanni Rotondo, Italy
| | - Evaristo Maiello
- grid.413503.00000 0004 1757 9135Department of Oncology, Fondazione “Casa Sollievo della Sofferenza” IRCCS Hospital, Viale Cappuccini 1, FG 71013 San Giovanni Rotondo, Italy
| | - Francesca Bazzocchi
- grid.413503.00000 0004 1757 9135Department of Surgery, Fondazione “Casa Sollievo della Sofferenza” IRCCS Hospital, Viale Cappuccini 1, FG 71013 San Giovanni Rotondo, Italy
| | - Francesco Perri
- grid.413503.00000 0004 1757 9135Division of Gastroenterology, Fondazione “Casa Sollievo della Sofferenza” IRCCS Hospital, Viale Cappuccini 1, FG 71013 San Giovanni Rotondo, Italy
| |
Collapse
|
|
11
|
Mazer BL, Lee JW, Roberts NJ, Chu LC, Lennon AM, Klein AP, Eshleman JR, Fishman EK, Canto MI, Goggins MG, Hruban RH. Screening for pancreatic cancer has the potential to save lives, but is it practical? Expert Rev Gastroenterol Hepatol 2023; 17:555-574. [PMID: 37212770 PMCID: PMC10424088 DOI: 10.1080/17474124.2023.2217354] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2023] [Revised: 04/21/2023] [Accepted: 05/19/2023] [Indexed: 05/23/2023]
Abstract
INTRODUCTION Most patients with pancreatic cancer present with advanced stage, incurable disease. However, patients with high-grade precancerous lesions and many patients with low-stage disease can be cured with surgery, suggesting that early detection has the potential to improve survival. While serum CA19.9 has been a long-standing biomarker used for pancreatic cancer disease monitoring, its low sensitivity and poor specificity have driven investigators to hunt for better diagnostic markers. AREAS COVERED This review will cover recent advances in genetics, proteomics, imaging, and artificial intelligence, which offer opportunities for the early detection of curable pancreatic neoplasms. EXPERT OPINION From exosomes, to circulating tumor DNA, to subtle changes on imaging, we know much more now about the biology and clinical manifestations of early pancreatic neoplasia than we did just five years ago. The overriding challenge, however, remains the development of a practical approach to screen for a relatively rare, but deadly, disease that is often treated with complex surgery. It is our hope that future advances will bring us closer to an effective and financially sound approach for the early detection of pancreatic cancer and its precursors.
Collapse
Affiliation(s)
- Benjamin L. Mazer
- The Sol Goldman Pancreatic Cancer Research Center, the Johns Hopkins University School of Medicine, Baltimore, MD
- Department of Pathology, the Johns Hopkins University School of Medicine, Baltimore, MD
| | - Jae W. Lee
- The Sol Goldman Pancreatic Cancer Research Center, the Johns Hopkins University School of Medicine, Baltimore, MD
- Department of Pathology, the Johns Hopkins University School of Medicine, Baltimore, MD
| | - Nicholas J. Roberts
- The Sol Goldman Pancreatic Cancer Research Center, the Johns Hopkins University School of Medicine, Baltimore, MD
- Department of Pathology, the Johns Hopkins University School of Medicine, Baltimore, MD
- Department of Oncology, the Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Linda C. Chu
- Department of Radiology, the Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Anne Marie Lennon
- Department of Medicine, Division of Gastroenterology and Hepatology, the Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Alison P. Klein
- The Sol Goldman Pancreatic Cancer Research Center, the Johns Hopkins University School of Medicine, Baltimore, MD
- Department of Pathology, the Johns Hopkins University School of Medicine, Baltimore, MD
- Department of Oncology, the Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - James R. Eshleman
- The Sol Goldman Pancreatic Cancer Research Center, the Johns Hopkins University School of Medicine, Baltimore, MD
- Department of Pathology, the Johns Hopkins University School of Medicine, Baltimore, MD
- Department of Oncology, the Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Elliot K. Fishman
- Department of Radiology, the Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Marcia Irene Canto
- Department of Medicine, Division of Gastroenterology and Hepatology, the Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Michael G. Goggins
- The Sol Goldman Pancreatic Cancer Research Center, the Johns Hopkins University School of Medicine, Baltimore, MD
- Department of Pathology, the Johns Hopkins University School of Medicine, Baltimore, MD
- Department of Oncology, the Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Ralph H. Hruban
- The Sol Goldman Pancreatic Cancer Research Center, the Johns Hopkins University School of Medicine, Baltimore, MD
- Department of Pathology, the Johns Hopkins University School of Medicine, Baltimore, MD
- Department of Oncology, the Johns Hopkins University School of Medicine, Baltimore, MD, USA
| |
Collapse
|
|
12
|
Bagias G, Kanavidis P, Vailas M, Despotidis M, Sotiropoulou M, Katsaros I, Maroulis I, Filippou D, Schizas D. Surgical management of familial pancreatic cancer: a systematic review of the literature. ANZ J Surg 2022; 92:2816-2821. [PMID: 35758214 DOI: 10.1111/ans.17834] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2022] [Revised: 04/30/2022] [Accepted: 05/19/2022] [Indexed: 11/30/2022]
Abstract
BACKGROUND Pancreatic ductal adenocarcinoma (PDAC) is the third most common cause of cancer-related mortality. The fact that the vast majority of patients with PDAC are diagnosed at an advanced stage highlights the need of early diagnosis. As hereditary factors are associated with approximately 5% of all PDAC cases, a screening programme to these high-risk individuals (HRI) has been proposed. The aim of screening methods is to identify selected group of patients with morphological abnormalities at an early stage, in order to be treated promptly. In this study, we evaluate the surgical outcomes and the appropriateness of pancreatic resection in HRIs who were selected for screening. METHODS A systematic literature search of the PubMed, Embase, and Cochrane databases was performed. The clinicopathological features were recorded and evaluated. RESULTS Six studies were selected for data collection. A total number of 77 patients were identified. Twenty-one patients had a germline mutation, with CDKN2A being the most prominent one (15.6%). Distal pancreatectomy was the most common surgical procedure (42.8%), followed by pancreaticoduodenectomy (33.8%). The mean disease-free survival was 23.6 months and tumour recurrence occurred in 9 patients (11.7%). Disease-specific mortality was 17.8%, while overall mortality was 19.5%. The most frequently reported postoperative diagnosis was PDAC (28 cases, 38.9%), followed by IPMN (23 cases, 31.9%), whereas high-grade PanIN lesions were found in 13 patients (18.1%). CONCLUSION High-risk individuals for pancreatic cancer, who are eventually operated may have a relatively uneventful postoperative course, however the oncological outcomes are comparable to the general population.
Collapse
Affiliation(s)
- George Bagias
- Third Department of Surgery, National and Kapodistrian University of Athens, Attikon University Hospital, Athens, Greece
| | - Prodromos Kanavidis
- First Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece
| | - Michail Vailas
- First Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece
| | - Markos Despotidis
- First Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece
| | - Maria Sotiropoulou
- First Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece
| | - Ioannis Katsaros
- First Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece
| | - Ioannis Maroulis
- Department of Surgery, University of Patras Medical School, Patras, Greece
| | - Dimitrios Filippou
- Department of Anatomy and Surgical Anatomy, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Dimitrios Schizas
- First Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece
| |
Collapse
|
|
13
|
Tanaka H, Tamura K, Abe T, Yoshida T, Macgregor-Das A, Dbouk M, Blackford AL, Borges M, Lennon AM, He J, Burkhart R, Canto MI, Goggins M. Serum Carboxypeptidase Activity and Genotype-Stratified CA19-9 to Detect Early-Stage Pancreatic Cancer. Clin Gastroenterol Hepatol 2022; 20:2267-2275.e2. [PMID: 34648951 PMCID: PMC9001752 DOI: 10.1016/j.cgh.2021.10.008] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2021] [Revised: 09/27/2021] [Accepted: 10/05/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND AIMS Serum diagnostic markers of early-stage pancreatic ductal adenocarcinoma (PDAC) are needed, especially for stage I disease. As tumors grow and cause pancreatic atrophy, markers derived from pancreatic parenchyma such as serum carboxypeptidase A (CPA) activity lose diagnostic performance. We evaluated, with CA19-9, serum CPA as a marker of early pancreatic cancer. METHODS Serum CPA activity levels were measured in 345 controls undergoing pancreatic surveillance, divided into 2 sets, set 1 being used to establish a reference range. Variants within the CPA1 locus were sought for their association with pancreatic CPA1 expression to determine if such variants associated with serum CPA levels. A total of 190 patients with resectable PDAC were evaluated. RESULTS Among controls, those having 1 or more minor alleles of CPA1 variants rs6955723 or rs2284682 had significantly higher serum CPA levels than did those without (P = .001). None of the PDAC cases with pancreatic atrophy had an elevated CPA. Among 122 PDAC cases without atrophy, defining serum CPA diagnostic cutoffs by a subject's CPA1 variants yielded a diagnostic sensitivity of 18% at 99% specificity (95% confidence interval [CI], 11.7-26) (vs 11.1% sensitivity using a uniform diagnostic cutoff); combining CPA with variant-stratified CA19-9 yielded a sensitivity of 68.0% (95% CI, 59.0-76.2) vs 63.1% (95% CI, 53.9- 71.7) for CA19-9 alone; and among stage I PDAC cases, diagnostic sensitivity was 51.9% (95% CI, 31.9-71.3) vs 37.0% (95% CI, 19.4-57.6) for CA19-9 alone. In the validation control set, the variant-stratified diagnostic cutoff yielded a specificity of 98.2%. CONCLUSION Serum CPA activity has diagnostic utility before the emergence of pancreatic atrophy as a marker of localized PDAC, including stage I disease.
Collapse
Affiliation(s)
- Haruyoshi Tanaka
- Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland
| | - Koji Tamura
- Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland
| | - Toshiya Abe
- Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland
| | - Takeichi Yoshida
- Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland
| | - Anne Macgregor-Das
- Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland
| | - Mohamad Dbouk
- Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland
| | - Amanda L Blackford
- Department of Oncology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland
| | - Michael Borges
- Department of Surgery, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland
| | - Anne Marie Lennon
- Department of Surgery, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland; Department of Medicine, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland
| | - Jin He
- Department of Surgery, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland
| | - Richard Burkhart
- Department of Surgery, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland
| | - Marcia Irene Canto
- Department of Oncology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland; Department of Medicine, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland
| | - Michael Goggins
- Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland; Department of Oncology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland; Department of Medicine, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland.
| |
Collapse
|
|
14
|
Peters MLB, Eckel A, Lietz A, Seguin C, Mueller P, Hur C, Pandharipande PV. Genetic testing to guide screening for pancreatic ductal adenocarcinoma: Results of a microsimulation model. Pancreatology 2022; 22:760-769. [PMID: 35752568 PMCID: PMC9474673 DOI: 10.1016/j.pan.2022.05.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2021] [Revised: 05/16/2022] [Accepted: 05/19/2022] [Indexed: 01/21/2023]
Abstract
BACKGROUND First-degree relatives (FDRs) of patients with pancreatic ductal adenocarcinoma (PDAC) have elevated PDAC risk, partially due to germline genetic variants. We evaluated the potential effectiveness of genetic testing to target MRI-based screening among FDRs. METHODS We used a microsimulation model of PDAC, calibrated to Surveillance, Epidemiology, and End Results (SEER) data, to estimate the potential life expectancy (LE) gain of screening for each of the following groups of FDRs: individuals who test positive for each of eight variants associated with elevated PDAC risk (e.g., BRCA2, CDKN2A); individuals who test negative; and individuals who do not test. Screening was assumed to take place if LE gains were achievable. We simulated multiple screening approaches, defined by starting age and frequency. Sensitivity analysis evaluated changes in results given varying model assumptions. RESULTS For women, 92% of mutation carriers had projected LE gains from screening for PDAC, if screening strategies (start age, frequency) were optimized. Among carriers, LE gains ranged from 0.1 days (ATM+ women screened once at age 70) to 510 days (STK11+ women screened annually from age 40). For men, LE gains were projected for all mutation carriers, ranging from 0.2 days (BRCA1+ men screened once at age 70) to 620 days (STK11+ men screened annually from age 40). For men and women who did not undergo genetic testing, or for whom testing showed no variant, screening yielded small LE benefit (0-2.1 days). CONCLUSIONS Genetic testing of FDRs can inform targeted PDAC screening by identifying which FDRs may benefit.
Collapse
Affiliation(s)
- Mary Linton B Peters
- Division of Medical Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, USA.
| | - Andrew Eckel
- Institute for Technology Assessment, Massachusetts General Hospital, USA
| | - Anna Lietz
- Institute for Technology Assessment, Massachusetts General Hospital, USA
| | - Claudia Seguin
- Institute for Technology Assessment, Massachusetts General Hospital, USA
| | - Peter Mueller
- Institute for Technology Assessment, Massachusetts General Hospital, USA
| | - Chin Hur
- Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Current Affiliation: Division of Gastroenterology, Columbia University College of Physicians and Surgeons, USA
| | - Pari V Pandharipande
- Institute for Technology Assessment and Department of Radiology, Massachusetts General Hospital, USA
| |
Collapse
|
|
15
|
Vanek P, Urban O, Zoundjiekpon V, Falt P. Current Screening Strategies for Pancreatic Cancer. Biomedicines 2022; 10:biomedicines10092056. [PMID: 36140157 PMCID: PMC9495594 DOI: 10.3390/biomedicines10092056] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2022] [Revised: 08/17/2022] [Accepted: 08/19/2022] [Indexed: 11/16/2022] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a dreaded malignancy with a dismal 5-year survival rate despite maximal efforts on optimizing treatment strategies. Radical surgery is the only potential curative procedure. Unfortunately, the majority of patients are diagnosed with locally advanced or metastatic disease, which renders them ineligible for curative resection. Early detection of PDAC is thus considered to be the most effective way to improve survival. In this regard, pancreatic screening has been proposed to improve results by detecting asymptomatic stages of PDAC and its precursors. There is now evidence of benefits of systematic surveillance in high-risk individuals, and the current guidelines emphasize the potential of screening to affect overall survival in individuals with genetic susceptibility syndromes or familial occurrence of PDAC. Here we aim to summarize the current knowledge about screening strategies for PDAC, including the latest epidemiological data, risk factors, associated hereditary syndromes, available screening modalities, benefits, limitations, as well as management implications.
Collapse
|
|
16
|
Kandiah J, Lo T, Jin D, Melchior L, Krebs TL, Anand N, Ingram S, Krumholtz P, Pandya D, Trinidad A, Dong X(E, Seshadri R, Bauman J, Lee R, Frank RC. A Community-Based Pancreatic Cancer Screening Study in High-Risk Individuals: Preliminary Efficacy and Safety Results. Clin Transl Gastroenterol 2022; 13:e00516. [PMID: 35854467 PMCID: PMC9400932 DOI: 10.14309/ctg.0000000000000516] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2022] [Revised: 06/09/2022] [Accepted: 06/30/2022] [Indexed: 11/28/2022] Open
Abstract
INTRODUCTION Pancreatic cancer (PC) screening recommendations have been based on studies performed solely at high-volume academic centers. To make PC screening more widely available, community-based efforts are essential. We implemented a prospective PC screening study in the community of Fairfield County, CT, and report our early safety and efficacy results. METHODS Eligible individuals were enrolled into an investigator-initiated study and underwent a baseline and 3 annual magnetic resonance imagings/magnetic resonance cholangiopancreatographies (MRIs/MRCPs) with gadolinium, biannual blood donations for biobanking, and assessments for anxiety and depression. All MRIs were presented at a multidisciplinary board to determine whether further investigation was warranted. RESULTS Seventy-five individuals have been enrolled and 201 MRIs performed over a 2.6-year average length of follow-up. Abnormal pancreatic findings (predominantly small cysts) were detected in 58.7% of the participants. Among these, 6.7% underwent endoscopic ultrasound, with 1 case complicated by postprocedural pancreatitis. One surgical resection was performed on a 4.7-cm intraductal papillary mucinous neoplasm with a focus on low-grade pancreatic intraepithelial neoplasia. One incidental finding of fibrosing mediastinitis was detected. Anxiety and depression scores decreased over the course of this study from 21.4% to 5.4% and 10.7% to 3.6%, respectively. DISCUSSION This preliminary report supports the feasibility of performing MRI/magnetic resonance cholangiopancreatographies-based PC screening as part of a clinical trial in a community setting. A longer follow-up is needed to better assess safety and efficacy. To the best of our knowledge, this is the first report from a community-based PC screening effort ( clinicaltrials.gov ID: NCT03250078).
Collapse
Affiliation(s)
- Jonathan Kandiah
- Department of Gastroenterology and Hepatology, Nuvance Health, Danbury, Connecticut, USA
| | - Tammy Lo
- Department of Medicine, Nuvance Health, Danbury, Connecticut, USA
| | - Dugho Jin
- Department of Radiology, Nuvance Health, Danbury, Connecticut, USA
| | - Landon Melchior
- Department of Radiology, Nuvance Health, Danbury, Connecticut, USA
| | | | - Naveen Anand
- Department of Gastroenterology and Hepatology, Nuvance Health, Danbury, Connecticut, USA
| | - Susan Ingram
- Department of Genetics, Nuvance Health, Danbury, Connecticut, USA
| | | | - Deep Pandya
- Rudy L. Ruggles Biomedical Research Institute, Nuvance Health, Danbury, Connecticut, USA
| | - Antolin Trinidad
- Department of Psychiatry, Nuvance Health, Danbury, Connecticut, USA
| | | | | | - James Bauman
- Department of Radiology, Nuvance Health, Danbury, Connecticut, USA
| | - Ronald Lee
- Department of Radiology, Nuvance Health, Danbury, Connecticut, USA
| | - Richard C. Frank
- Department of Gastroenterology and Hepatology, Nuvance Health, Danbury, Connecticut, USA
- Rudy L. Ruggles Biomedical Research Institute, Nuvance Health, Danbury, Connecticut, USA
| |
Collapse
|
|
17
|
Ardeshna DR, Rangwani S, Cao T, Pawlik TM, Stanich PP, Krishna SG. Intraductal Papillary Mucinous Neoplasms in Hereditary Cancer Syndromes. Biomedicines 2022; 10:1475. [PMID: 35884779 PMCID: PMC9313108 DOI: 10.3390/biomedicines10071475] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2022] [Revised: 06/17/2022] [Accepted: 06/20/2022] [Indexed: 11/16/2022] Open
Abstract
Hereditary pancreatic cancer, which includes patients with familial pancreatic cancer (FPC) and hereditary pancreatic cancer syndromes, accounts for about 10% of all pancreatic cancer diagnoses. The early detection of pre-cancerous pancreatic cysts has increasingly become a focus of interest in recent years as a potential avenue to lower pancreatic cancer incidence and mortality. Intraductal papillary mucinous cystic neoplasms (IPMNs) are recognized precursor lesions of pancreatic cancer. IPMNs have high prevalence in patients with hereditary pancreatic cancer and their relatives. While various somatic mutations have been identified in IPMNs, certain germline mutations associated with hereditary cancer syndromes have also been identified in IPMNs, suggesting a role in their formation. While the significance for the higher prevalence of IPMNs or similar germline mutations in these high-risk patients remain unclear, IPMNs do represent pre-malignant lesions that need close surveillance. This review summarizes the available literature on the incidence and prevalence of IPMNs in inherited genetic predisposition syndromes and FPC and speculates if IPMN and pancreatic cancer surveillance in these high-risk individuals needs to change.
Collapse
Affiliation(s)
- Devarshi R. Ardeshna
- Department of Internal Medicine, Ohio State University Wexner Medical Center, Columbus, OH 43210, USA; (D.R.A.); (S.R.)
| | - Shiva Rangwani
- Department of Internal Medicine, Ohio State University Wexner Medical Center, Columbus, OH 43210, USA; (D.R.A.); (S.R.)
| | - Troy Cao
- College of Medicine, Ohio State University, Columbus, OH 43210, USA;
| | - Timothy M. Pawlik
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA;
| | - Peter P. Stanich
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA;
| | - Somashekar G. Krishna
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA;
| |
Collapse
|
|
18
|
Wang Y, Cuggia A, Chen YI, Parent J, Stanek A, Denroche RE, Zhang A, Grant RC, Domecq C, Golesworthy B, Shwaartz C, Borgida A, Holter S, Wilson JM, Chong G, O'Kane GM, Knox JJ, Fischer SE, Gallinger S, Gao ZH, Foulkes WD, Waschke KA, Zogopoulos G. Is Biannual Surveillance for Pancreatic Cancer Sufficient in Individuals With Genetic Syndromes or Familial Pancreatic Cancer? J Natl Compr Canc Netw 2022; 20:663-673.e12. [PMID: 35714671 DOI: 10.6004/jnccn.2021.7107] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2021] [Accepted: 10/26/2021] [Indexed: 11/17/2022]
Abstract
BACKGROUND Individuals with a family history of pancreatic adenocarcinoma (PC) or with a germline mutation in a PC susceptibility gene are at increased risk of developing PC. These high-risk individuals (HRIs) may benefit from PC surveillance. METHODS A PC surveillance program was developed to evaluate the detection of premalignant lesions and early-stage PCs using biannual imaging and to determine whether locally advanced or metastatic PCs develop despite biannual surveillance. From January 2013 to April 2020, asymptomatic HRIs were enrolled and followed with alternating MRI and endoscopic ultrasound every 6 months. RESULTS Of 75 HRIs, 43 (57.3%) had a germline mutation in a PC susceptibility gene and 32 (42.7%) had a familial pancreatic cancer (FPC) pedigree. Branch-duct intraductal papillary mucinous neoplasms (BD-IPMNs) were identified in 26 individuals (34.7%), but only 2 developed progressive lesions. One patient with Peutz-Jeghers syndrome (PJS) developed locally advanced PC arising from a BD-IPMN. Whole-genome sequencing of this patient's PC and of a second patient with PJS-associated PC from the same kindred revealed biallelic inactivation of STK11 in a KRAS-independent manner. A review of 3,853 patients from 2 PC registries identified an additional patient with PJS-associated PC. All 3 patients with PJS developed advanced PC consistent with the malignant transformation of an underlying BD-IPMN in <6 months. The other surveillance patient with a progressive lesion had FPC and underwent resection of a mixed-type IPMN that harbored polyclonal KRAS mutations. CONCLUSIONS PC surveillance identifies a high prevalence of BD-IPMNs in HRIs. Patients with PJS with BD-IPMNs may be at risk for accelerated malignant transformation.
Collapse
Affiliation(s)
- Yifan Wang
- Department of Surgery, McGill University, Montreal, Quebec
- Research Institute of the McGill University Health Centre, Montreal, Quebec
- Rosalind and Morris Goodman Cancer Institute
| | - Adeline Cuggia
- Research Institute of the McGill University Health Centre, Montreal, Quebec
- Rosalind and Morris Goodman Cancer Institute
| | - Yen-I Chen
- Research Institute of the McGill University Health Centre, Montreal, Quebec
- Division of Gastroenterology and Hepatology, and
| | - Josée Parent
- Division of Gastroenterology and Hepatology, and
| | - Agatha Stanek
- Research Institute of the McGill University Health Centre, Montreal, Quebec
- Department of Diagnostic Radiology, McGill University, Montreal, Quebec
| | | | - Amy Zhang
- Ontario Institute for Cancer Research, Toronto, Ontario
| | - Robert C Grant
- Ontario Institute for Cancer Research, Toronto, Ontario
- Wallace McCain Centre for Pancreatic Cancer, Princess Margaret Cancer Centre, Toronto, Ontario
| | - Céline Domecq
- Research Institute of the McGill University Health Centre, Montreal, Quebec
- Rosalind and Morris Goodman Cancer Institute
| | - Bryn Golesworthy
- Research Institute of the McGill University Health Centre, Montreal, Quebec
- Rosalind and Morris Goodman Cancer Institute
| | - Chaya Shwaartz
- Wallace McCain Centre for Pancreatic Cancer, Princess Margaret Cancer Centre, Toronto, Ontario
| | - Ayelet Borgida
- Ontario Pancreas Cancer Study, Mount Sinai Hospital, Toronto, Ontario
| | - Spring Holter
- Ontario Institute for Cancer Research, Toronto, Ontario
| | | | - George Chong
- Molecular Diagnostics Laboratory, Sir Mortimer B. Davis-Jewish General Hospital, Montreal, Quebec
| | - Grainne M O'Kane
- Wallace McCain Centre for Pancreatic Cancer, Princess Margaret Cancer Centre, Toronto, Ontario
| | - Jennifer J Knox
- Wallace McCain Centre for Pancreatic Cancer, Princess Margaret Cancer Centre, Toronto, Ontario
| | | | - Steven Gallinger
- Ontario Institute for Cancer Research, Toronto, Ontario
- Wallace McCain Centre for Pancreatic Cancer, Princess Margaret Cancer Centre, Toronto, Ontario
- Ontario Pancreas Cancer Study, Mount Sinai Hospital, Toronto, Ontario
| | | | - William D Foulkes
- Research Institute of the McGill University Health Centre, Montreal, Quebec
- Department of Human Genetics, and
- Lady Davis Institute for Medical Research, McGill University, Montreal, Quebec, Canada
| | | | - George Zogopoulos
- Department of Surgery, McGill University, Montreal, Quebec
- Research Institute of the McGill University Health Centre, Montreal, Quebec
- Rosalind and Morris Goodman Cancer Institute
| |
Collapse
|
|
19
|
Overbeek KA, Levink IJM, Koopmann BDM, Harinck F, Konings ICAW, Ausems MGEM, Wagner A, Fockens P, van Eijck CH, Groot Koerkamp B, Busch ORC, Besselink MG, Bastiaansen BAJ, van Driel LMJW, Erler NS, Vleggaar FP, Poley JW, Cahen DL, van Hooft JE, Bruno MJ. Long-term yield of pancreatic cancer surveillance in high-risk individuals. Gut 2022; 71:1152-1160. [PMID: 33820756 PMCID: PMC9120399 DOI: 10.1136/gutjnl-2020-323611] [Citation(s) in RCA: 95] [Impact Index Per Article: 31.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2020] [Revised: 03/20/2021] [Accepted: 03/22/2021] [Indexed: 12/11/2022]
Abstract
OBJECTIVE We aimed to determine the long-term yield of pancreatic cancer surveillance in hereditary predisposed high-risk individuals. DESIGN From 2006 to 2019, we prospectively enrolled asymptomatic individuals with an estimated 10% or greater lifetime risk of pancreatic ductal adenocarcinoma (PDAC) after obligatory evaluation by a clinical geneticist and genetic testing, and subjected them to annual surveillance with both endoscopic ultrasonography (EUS) and MRI/cholangiopancreatography (MRI/MRCP) at each visit. RESULTS 366 individuals (201 mutation-negative familial pancreatic cancer (FPC) kindreds and 165 PDAC susceptibility gene mutation carriers; mean age 54 years, SD 9.9) were followed for 63 months on average (SD 43.2). Ten individuals developed PDAC, of which four presented with a symptomatic interval carcinoma and six underwent resection. The cumulative PDAC incidence was 9.3% in the mutation carriers and 0% in the FPC kindreds (p<0.001). Median PDAC survival was 18 months (range 1-32). Surgery was performed in 17 individuals (4.6%), whose pathology revealed 6 PDACs (3 T1N0M0), 7 low-grade precursor lesions, 2 neuroendocrine tumours <2 cm, 1 autoimmune pancreatitis and in 1 individual no abnormality. There was no surgery-related mortality. EUS detected more solid lesions than MRI/MRCP (100% vs 22%, p<0.001), but less cystic lesions (42% vs 83%, p<0.001). CONCLUSION The diagnostic yield of PDAC was substantial in established high-risk mutation carriers, but non-existent in the mutation-negative proven FPC kindreds. Nevertheless, timely identification of resectable lesions proved challenging despite the concurrent use of two imaging modalities, with EUS outperforming MRI/MRCP. Overall, surveillance by imaging yields suboptimal results with a clear need for more sensitive diagnostic markers, including biomarkers.
Collapse
Affiliation(s)
- Kasper A Overbeek
- Department of Gastroenterology & Hepatology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Iris J M Levink
- Department of Gastroenterology & Hepatology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Brechtje D M Koopmann
- Department of Gastroenterology & Hepatology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Femme Harinck
- Department of Gastroenterology & Hepatology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Ingrid C A W Konings
- Department of Gastroenterology & Hepatology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Margreet G E M Ausems
- Division Laboratories, Pharmacy and Biomedical Genetics, Department of Genetics, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Anja Wagner
- Department of Clinical Genetics, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Paul Fockens
- Department of Gastroenterology & Hepatology, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Casper H van Eijck
- Department of Surgery, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Bas Groot Koerkamp
- Department of Surgery, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Olivier R C Busch
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Marc G Besselink
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Barbara A J Bastiaansen
- Department of Gastroenterology & Hepatology, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Lydi M J W van Driel
- Department of Gastroenterology & Hepatology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Nicole S Erler
- Department of Biostatistics, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Frank P Vleggaar
- Department of Gastroenterology & Hepatology, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Jan-Werner Poley
- Department of Gastroenterology & Hepatology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Djuna L Cahen
- Department of Gastroenterology & Hepatology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Jeanin E van Hooft
- Department of Gastroenterology & Hepatology, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Marco J Bruno
- Department of Gastroenterology & Hepatology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands
| |
Collapse
|
|
20
|
Kumar S, Santos RJ, McGuigan AJ, Singh U, Johnson P, Kunzmann AT, Turkington RC. The Role of Circulating Protein and Metabolite Biomarkers in the Development of Pancreatic Ductal Adenocarcinoma (PDAC): A Systematic Review and Meta-analysis. Cancer Epidemiol Biomarkers Prev 2022; 31:1090-1102. [PMID: 34810209 PMCID: PMC9377754 DOI: 10.1158/1055-9965.epi-21-0616] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2021] [Revised: 08/19/2021] [Accepted: 11/08/2021] [Indexed: 01/07/2023] Open
Abstract
BACKGROUND Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, and this is attributed to it being diagnosed at an advanced stage. Understanding the pathways involved in initial development may improve early detection strategies. This systematic review assessed the association between circulating protein and metabolite biomarkers and PDAC development. METHODS A literature search until August 2020 in MEDLINE, EMBASE, and Web of Science was performed. Studies were included if they assessed circulating blood, urine, or salivary biomarkers and their association with PDAC risk. Quality was assessed using the Newcastle-Ottawa scale for cohort studies. Random-effects meta-analyses were used to calculate pooled relative risk. RESULTS A total of 65 studies were included. Higher levels of glucose were found to be positively associated with risk of developing PDAC [n = 4 studies; pooled relative risk (RR): 1.61; 95% CI: 1.16-2.22]. Additionally, an inverse association was seen with pyridoxal 5'-phosphate (PLP) levels (n = 4 studies; RR: 0.62; 95% CI: 0.44-0.87). Meta-analyses showed no association between levels of C-peptide, members of the insulin growth factor signaling pathway, C-reactive protein, adiponectin, 25-hydroxyvitamin D, and folate/homocysteine and PDAC risk. Four individual studies also reported a suggestive positive association of branched-chain amino acids with PDAC risk, but due to differences in measures reported, a meta-analysis could not be performed. CONCLUSIONS Our pooled analysis demonstrates that higher serum glucose levels and lower levels of PLP are associated with risk of PDAC. IMPACT Glucose and PLP levels are associated with PDAC risk. More prospective studies are required to identify biomarkers for early detection.
Collapse
Affiliation(s)
- Swati Kumar
- Patrick G Johnston Centre for Cancer Research, Queen's University Belfast, Belfast, Northern Ireland, United Kingdom
| | - Ralph J. Santos
- Centre for Public Health, Queen's University Belfast, Belfast, Northern Ireland, United Kingdom
| | - Andrew J. McGuigan
- Patrick G Johnston Centre for Cancer Research, Queen's University Belfast, Belfast, Northern Ireland, United Kingdom
| | - Urvashi Singh
- Patrick G Johnston Centre for Cancer Research, Queen's University Belfast, Belfast, Northern Ireland, United Kingdom
| | - Peter Johnson
- Patrick G Johnston Centre for Cancer Research, Queen's University Belfast, Belfast, Northern Ireland, United Kingdom
| | - Andrew T. Kunzmann
- Centre for Public Health, Queen's University Belfast, Belfast, Northern Ireland, United Kingdom
| | - Richard C. Turkington
- Patrick G Johnston Centre for Cancer Research, Queen's University Belfast, Belfast, Northern Ireland, United Kingdom
| |
Collapse
|
|
21
|
Calderwood AH, Sawhney MS, Thosani NC, Rebbeck TR, Wani S, Canto MI, Fishman DS, Golan T, Hidalgo M, Kwon RS, Riegert-Johnson DL, Sahani DV, Stoffel EM, Vollmer CM, Al-Haddad MA, Amateau SK, Buxbaum JL, DiMaio CJ, Fujii-Lau LL, Jamil LH, Jue TL, Law JK, Lee JK, Naveed M, Pawa S, Storm AC, Qumseya BJ. American Society for Gastrointestinal Endoscopy guideline on screening for pancreatic cancer in individuals with genetic susceptibility: methodology and review of evidence. Gastrointest Endosc 2022; 95:827-854.e3. [PMID: 35183359 DOI: 10.1016/j.gie.2021.12.002] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/24/2021] [Accepted: 12/02/2021] [Indexed: 02/08/2023]
Affiliation(s)
- Audrey H Calderwood
- Section of Gastroenterology and Hepatology, Dartmouth-Hitchcock Medical Center, Dartmouth Geisel School of Medicine, Lebanon, New Hampshire, USA
| | - Mandeep S Sawhney
- Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Nirav C Thosani
- Center for Interventional Gastroenterology at UTHealth, McGovern Medical School, Houston, Texas, USA
| | - Timothy R Rebbeck
- Harvard TH Chan School of Public Health and Dana-Farber Cancer Institute, Boston, Massachusetts, USA
| | - Sachin Wani
- Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Marcia I Canto
- Division of Gastroenterology and Hepatology, Johns Hopkins Medicine, Baltimore, Maryland, USA
| | - Douglas S Fishman
- Section of Pediatric Gastroenterology, Hepatology and Nutrition, Baylor College of Medicine, Texas Children's Hospital, Houston, Texas, USA
| | - Talia Golan
- Cancer Center, Sheba Medical Center, Yehuda, Israel
| | - Manuel Hidalgo
- Division of Hematology and Oncology, Weill Cornell Medicine, New York, New York, USA
| | - Richard S Kwon
- Division of Gastroenterology, Michigan Medicine, University of Michigan, Ann Arbor, Michigan, USA
| | - Douglas L Riegert-Johnson
- Department of Clinical Genomics and Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida, USA
| | - Dushyant V Sahani
- Department of Radiology, University of Washington, Seattle, Washington, USA
| | - Elena M Stoffel
- Division of Gastroenterology, Michigan Medicine, University of Michigan, Ann Arbor, Michigan, USA
| | - Charles M Vollmer
- Department of Surgery, Penn Medicine, Philadelphia, Pennsylvania, USA
| | - Mohammad A Al-Haddad
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - Stuart K Amateau
- Division of Gastroenterology Hepatology and Nutrition, University of Minnesota Medical Center, Minneapolis, Minnesota, USA
| | - James L Buxbaum
- Division of Gastrointestinal and Liver Diseases, Keck School of Medicine of University of Southern California, Los Angeles, California, USA
| | - Christopher J DiMaio
- Department of Gastroenterology, Mount Sinai School of Medicine, New York, New York, USA
| | - Larissa L Fujii-Lau
- Department of Gastroenterology, The Queen's Medical Center, Honolulu, Hawaii, USA
| | - Laith H Jamil
- Section of Gastroenterology and Hepatology, Beaumont Health, Royal Oak, Michigan, and Oakland University William Beaumont School of Medicine, Rochester, Michigan, USA
| | - Terry L Jue
- Department of Gastroenterology, The Permanente Medical Group, San Francisco, California, USA
| | - Joanna K Law
- Department of Gastroenterology and Hepatology, Digestive Disease Institute, Virginia Mason Medical Center, Seattle, Washington, USA
| | - Jeffrey K Lee
- Department of Gastroenterology, Kaiser Permanente San Francisco Medical Center, San Francisco, California, USA
| | - Mariam Naveed
- Advent Health Medical Group, Gastroenterology/Hepatology, Advent Health Hospital Altamonte Springs, Altamonte Springs, Florida, USA
| | - Swati Pawa
- Department of Gastroenterology, Wake Forest School of Medicine, Winston Salem, North Carolina, USA
| | - Andrew C Storm
- Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Bashar J Qumseya
- Department of Gastroenterology, Hepatology and Nutrition, University of Florida, Gainesville, Florida, USA
| |
Collapse
|
|
22
|
Sawhney MS, Calderwood AH, Thosani NC, Rebbeck TR, Wani S, Canto MI, Fishman DS, Golan T, Hidalgo M, Kwon RS, Riegert-Johnson DL, Sahani DV, Stoffel EM, Vollmer CM, Qumseya BJ. ASGE guideline on screening for pancreatic cancer in individuals with genetic susceptibility: summary and recommendations. Gastrointest Endosc 2022; 95:817-826. [PMID: 35183358 DOI: 10.1016/j.gie.2021.12.001] [Citation(s) in RCA: 61] [Impact Index Per Article: 20.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/24/2021] [Accepted: 12/02/2021] [Indexed: 12/11/2022]
Affiliation(s)
- Mandeep S Sawhney
- Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Audrey H Calderwood
- Section of Gastroenterology and Hepatology, Dartmouth-Hitchcock Medical Center, Dartmouth Geisel School of Medicine, Lebanon, New Hampshire, USA
| | - Nirav C Thosani
- Center for Interventional Gastroenterology at UT Health, McGovern Medical School, Houston, Texas, USA
| | - Timothy R Rebbeck
- Harvard TH Chan School of Public Health and Dana-Farber Cancer Institute, Boston, Massachusetts, USA
| | - Sachin Wani
- Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Marcia I Canto
- Division of Gastroenterology and Hepatology, Johns Hopkins Medicine, Baltimore, Maryland, USA
| | - Douglas S Fishman
- Section of Pediatric Gastroenterology, Hepatology and Nutrition, Baylor College of Medicine, Texas Children's Hospital, Houston, Texas, USA
| | - Talia Golan
- Oncology Institute, Sheba Medical Center, Tel Aviv University, Tel Aviv, Israel
| | - Manuel Hidalgo
- Division of Hematology and Oncology, Weill Cornell Medicine, New York, New York, USA
| | - Richard S Kwon
- Division of Gastroenterology, Michigan Medicine, University of Michigan, Ann Arbor, Michigan, USA
| | - Douglas L Riegert-Johnson
- Department of Clinical Genomics and Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida, USA
| | - Dushyant V Sahani
- Department of Radiology, University of Washington, Seattle, Washington, USA
| | - Elena M Stoffel
- Division of Gastroenterology, Michigan Medicine, University of Michigan, Ann Arbor, Michigan, USA
| | - Charles M Vollmer
- Department of Surgery, Penn Medicine, Philadelphia, Pennsylvania, USA
| | - Bashar J Qumseya
- Department of Gastroenterology, Hepatology and Nutrition, University of Florida, Gainesville, Florida, USA
| |
Collapse
|
|
23
|
Hijioka S, Morizane C, Takaori K, Okusaka T. Study protocol for a multi-institutional prospective surveillance study among kindreds with familial pancreatic cancer and individuals with hereditary pancreatic cancer syndrome: The Diamond Study. Pancreatology 2022; 22:534-538. [PMID: 35443912 DOI: 10.1016/j.pan.2022.04.006] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2022] [Revised: 04/08/2022] [Accepted: 04/12/2022] [Indexed: 12/11/2022]
Abstract
BACKGROUND Family history of pancreatic cancer (PC) and some hereditary cancer syndromes are risk factors for PC. Previous studies suggest that conducting surveillance for kindreds at high risk for familial PC may be useful for diagnoses at the stage where resections can still be implemented; however, there is insufficient evidence linking surveillance and increased rates of resectable PC. METHODS We launched a surveillance study for kindreds with familial PC and individuals with hereditary PC syndrome, titled the "Diamond Study," in June 2020. This Japanese national multi-institutional prospective intervention study has been initiated to conduct evaluations within a prospective clinical trial format. RESULTS The primary endpoint is the fraction of patients with resectable PC among patients with PC found through surveillance interventions. Endoscopic ultrasound and magnetic resonance imaging combined with magnetic resonance cholangiopancreatography will be performed alternatively every 6 months for up to 15 years, with 400 as the predicted number of registered participants and a predicted registration period of 10 years. CONCLUSION We intend to scientifically prove the usefulness of surveillance for kindreds with familial PC and individuals with hereditary PC syndrome to improve PC prognoses.
Collapse
Affiliation(s)
- Susumu Hijioka
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan.
| | - Chigusa Morizane
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan
| | | | - Takuji Okusaka
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan
| |
Collapse
|
|
24
|
Gonda TA, Farrell J, Wallace M, Khanna L, Janec E, Kwon R, Saunders M, Siddiqui UD, Brand R, Simeone DM. Standardization of EUS imaging and reporting in high-risk individuals of pancreatic adenocarcinoma: consensus statement of the Pancreatic Cancer Early Detection Consortium. Gastrointest Endosc 2022; 95:723-732.e7. [PMID: 34736932 DOI: 10.1016/j.gie.2021.10.025] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2021] [Accepted: 10/25/2021] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIMS Pancreatic ductal adenocarcinoma is an aggressive disease most often diagnosed after local progression or metastatic dissemination, precluding resection and resulting in a high mortality rate. For individuals with elevated personal risk of the development of pancreatic cancer, EUS is a frequently used advanced imaging and diagnostic modality. However, variability in the expertise and definition of EUS findings exists among gastroenterologists, as well as a lack of standardized reporting of relevant findings at the time of examination. Adoption of standardized EUS reporting, using a universally accepted and agreed on terminology, is needed. METHODS A consensus statement designed to create a standardized reporting template was authored by a multidisciplinary group of experts in pancreatic diseases that includes gastroenterologists, radiologists, surgeons, oncologists, and geneticists. This statement was developed using a modified Delphi process as part of the Pancreatic Cancer Early Detection Consortium, and >75% agreement was required to reach consensus. RESULTS We identified reporting elements and present standardized reporting templates for EUS indications, procedural data, EUS image capture, and descriptors of findings, tissue sampling, and postprocedural assessment of adequacy. CONCLUSIONS Adoption of this standardized EUS reporting template should improve consistency in clinical decision-making for individuals with elevated risk of pancreatic cancer by providing complete and accurate reporting of pancreatic abnormalities. Standardization will also help to facilitate research and clinical trial design by using clearly defined and consistent imaging descriptions, thus allowing for comparison of results across different centers.
Collapse
Affiliation(s)
- Tamas A Gonda
- Division of Gastroenterology and Hepatology, New York University Langone Health, New York, New York, USA
| | - James Farrell
- Department of Medicine, Yale University School of Medicine, New Haven, Connecticut, USA
| | - Michael Wallace
- Department of Gastroenterology & Hepatology, Mayo Clinic, Jacksonville, Florida, USA
| | - Lauren Khanna
- Division of Gastroenterology and Hepatology, New York University Langone Health, New York, New York, USA
| | - Eileen Janec
- Division of Gastroenterology and Hepatology, New York University Langone Health, New York, New York, USA
| | - Richard Kwon
- Gastroenterology, Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
| | - Michael Saunders
- Gastroenterology, Internal Medicine, University of Washington, Seattle, Washington, USA
| | - Uzma D Siddiqui
- Gastroenterology, Internal Medicine, University of Chicago, Chicago, Illinois, USA
| | - Randall Brand
- Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Diane M Simeone
- Gastroenterology, Surgical Oncology, New York University Langone Health, New York, New York, USA
| |
Collapse
|
|
25
|
Connor AA, Gallinger S. Pancreatic cancer evolution and heterogeneity: integrating omics and clinical data. Nat Rev Cancer 2022; 22:131-142. [PMID: 34789870 DOI: 10.1038/s41568-021-00418-1] [Citation(s) in RCA: 167] [Impact Index Per Article: 55.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/18/2021] [Indexed: 12/15/2022]
Abstract
Pancreatic ductal adenocarcinoma (PDAC), already among the deadliest epithelial malignancies, is rising in both incidence and contribution to overall cancer deaths. Decades of research have improved our understanding of PDAC carcinogenesis, including characterizing germline predisposition, the cell of origin, precursor lesions, the sequence of genetic alterations, including simple and structural alterations, transcriptional changes and subtypes, tumour heterogeneity, metastatic progression and the tumour microenvironment. These fundamental advances inform contemporary translational efforts in primary prevention, screening and early detection, multidisciplinary management and survivorship, as prospective clinical trials begin to adopt molecular-based selection criteria to guide targeted therapies. Genomic and transcriptomic data on PDAC were also included in the international pan-cancer analysis of approximately 2,600 cancers, a milestone in cancer research that allows further insight through comparison with other tumour types. Thus, this is an ideal time to review our current knowledge of PDAC evolution and heterogeneity, gained from the study of preclinical models and patient biospecimens, and to propose a model of PDAC evolution that takes into consideration findings from varied sources, with a particular focus on the genomics of human PDAC.
Collapse
Affiliation(s)
- Ashton A Connor
- Department of Surgery, Houston Methodist Hospital, Houston, TX, USA
| | - Steven Gallinger
- Hepatobiliary/Pancreatic Surgical Oncology Program, University Health Network, Toronto, ON, Canada.
- PanCuRx Translational Research Initiative, Ontario Institute for Cancer Research, Toronto, ON, Canada.
- Wallace McCain Centre for Pancreatic Cancer, Princess Margaret Hospital Cancer Centre, Toronto, ON, Canada.
- Ontario Pancreas Cancer Study, Mount Sinai Hospital, Toronto, ON, Canada.
| |
Collapse
|
|
26
|
Chhoda A, Vodusek Z, Wattamwar K, Mukherjee E, Gunderson C, Grimshaw A, Sharma A, Ahuja N, Kastrinos F, Farrell JJ. Late-Stage Pancreatic Cancer Detected During High-Risk Individual Surveillance: A Systematic Review and Meta-Analysis. Gastroenterology 2022; 162:786-798. [PMID: 34813861 DOI: 10.1053/j.gastro.2021.11.021] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2021] [Revised: 10/15/2021] [Accepted: 11/09/2021] [Indexed: 12/13/2022]
Abstract
BACKGROUND & AIMS Identification and resection of successful targets, that is, T1 N0M0 pancreatic ductal adenocarcinoma (PDAC) and high-grade precursors during surveillance of high-risk individuals (HRIs) confers improved survival. Late-stage PDACs refer to T2-4 N0M0 and nodal or distant metastatic PDAC stages diagnosed during the follow-up phase of HRI surveillance. This study aimed to quantify late-stage PDACs during HRI surveillance and identify associated clinicoradiologic factors. METHODS A systematic search (PROSPERO:CRD42018117189) from Cochrane Library, Embase, Google Scholar, Medline, PubMed, Scopus, and Web of Science was last performed on April 18, 2021. Only original HRI surveillance manuscripts that specified follow-up strategies were included, and studies with only baseline information were excluded. Cumulative incidences of advanced neoplasia: high-grade precursors and all PDACs, and surveillance-detected/interval late-stage PDACs were calculated through random-effects model. Incidence of late-stage PDACs underwent metaregression to identify association with HRI clinicoradiologic features. Publication bias was assessed through the funnel plot and Egger's regression line. RESULTS Thirteen original surveillance studies included 2169 HRIs followed over 7302.72 patient-years. Cumulative incidence of advanced neoplasia and late-stage PDACs was 3.3 (95% confidence interval [CI]: 0.6-7.4) and 1.7 (95% CI: 0.2-4.0) per 1000 patient-years, respectively. Late-stage PDACs lacked significant association with surveillance imaging, baseline pancreatic morphology, study location, genetic background, gender, or age. Limited information on diagnostic error, symptoms, timing of presentation, lesion site, and surveillance adherence precluded formal meta-analysis. CONCLUSION A sizeable proportion of late-stage PDACs were detected during follow-up. Their incidence lacked association with baseline clinicoradiologic features. Further causal investigation of stage-based outcomes is warranted for overall improvement in HRI surveillance.
Collapse
Affiliation(s)
| | - Ziga Vodusek
- Department of Internal Medicine, RWJ School of Medicine, New Brunswick, New Jersey
| | - Kapil Wattamwar
- Department of Radiology, Albert Einstein College of Medicine, Bronx, New York
| | - Eric Mukherjee
- Department of Dermatology, Vanderbilt University, Nashville, Tennessee
| | - Craig Gunderson
- Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut
| | - Alyssa Grimshaw
- Cushing/Whitney Medical Library, Yale University, New Haven, Connecticut
| | - Anup Sharma
- Department of Surgery, Yale School of Medicine, New Haven, Connecticut
| | - Nita Ahuja
- Yale School of Medicine, New Haven, Connecticut
| | - Fay Kastrinos
- Columbia University Medical Center, New York, New York
| | - James J Farrell
- Department of Digestive Diseases, Yale School of Medicine, New Haven, Connecticut.
| |
Collapse
|
|
27
|
Cai J, Chen H, Lu M, Zhang Y, Lu B, You L, Zhang T, Dai M, Zhao Y. Advances in the epidemiology of pancreatic cancer: Trends, risk factors, screening, and prognosis. Cancer Lett 2021; 520:1-11. [PMID: 34216688 DOI: 10.1016/j.canlet.2021.06.027] [Citation(s) in RCA: 193] [Impact Index Per Article: 48.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2021] [Revised: 06/09/2021] [Accepted: 06/25/2021] [Indexed: 02/07/2023]
Abstract
Pancreatic cancer is a malignancy with poor prognosis and high mortality. The recent increase in pancreatic cancer incidence and mortality has resulted in an increased number of studies on its epidemiology. This comprehensive and systematic literature review summarizes the advances in the epidemiology of pancreatic cancer, including its epidemiological trends, risk factors, risk prediction models, screening modalities, and prognosis. The risk factors for pancreatic cancers can be categorized as those related to individual characteristics, lifestyle and environment, and disease status. Several prediction models for pancreatic cancer have been developed in populations with new-onset diabetes or a family history of pancreatic cancer; however, these models require further validation. Despite recent progress in pancreatic cancer screening, the quantity and quality of related studies are also unsatisfactory, especially with respect to the identification of high-risk populations and development of effective screening modality. Apart from the populations with familial genetic risk and those at a high risk of sporadic pancreatic cancer, risk factors such as new-onset diabetes may be a new direction for timely intervention. We hope this work will provide new ideas for further prevention and treatment of pancreatic cancer.
Collapse
Affiliation(s)
- Jie Cai
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China
| | - Hongda Chen
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100021, China
| | - Ming Lu
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100021, China
| | - Yuhan Zhang
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100021, China
| | - Bin Lu
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100021, China
| | - Lei You
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China
| | - Taiping Zhang
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China
| | - Min Dai
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100021, China.
| | - Yupei Zhao
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China.
| |
Collapse
|
|
28
|
Abstract
Screening for pancreatic cancer (PC) in high-risk groups aimed to detect early cancers is currently done only in the research setting, and data on psychological outcomes of screening in these populations is scarce. To determine the psychological impact of a national Australian pancreatic screening program, a prospective study was conducted using validated psychological measures: impact of events scale (IES), psychological consequences questionnaire (PCQ) and the cancer worry scale. Measures were administered at baseline, 1-month and at 1-year post-enrolment and correlations with abnormal endoscopic ultrasound (EUS) results were calculated. Over a 6-year period, 102 participants were recruited to the screening program. Thirty-nine patients (38.2%) had an abnormal endoscopic ultrasound, and two patients (2.0%) were diagnosed with PC and two with other malignancies. Those with a personal history of cancer or a positive BRCA2 mutation demonstrated significantly increased worry about developing other types of cancer at baseline (p < 0.01). Irrespective of EUS result, there was a significant decrease of total IES score at 1 year (Z = - 2.0, p = 0.041). In patients with abnormal EUS results, there was a decrease in the total IES score at 1 year (Z = - 2.5, p = 0.011). In participants deemed to be most distressed at baseline based on their negative PCQ score, there was a significant decrease of the total PCQ (Z = - 3.2, p = 0.001), emotional (Z = - 3.0, p = 0.001), social (Z = 3.0, p = 0.001) and physical (Z = - 2.8, p = 0.002) subscale at 1-year post-intervention. This study provides evidence of the long-term psychological benefits of PC screening in high-risk patients. There was no negative impact of screening in the short-term and the positive benefits appeared at 1-year post-intervention irrespective of screening result.
Collapse
|
|
29
|
Kogekar N, Diaz KE, Weinberg AD, Lucas AL. Surveillance of high-risk individuals for pancreatic cancer with EUS and MRI: A meta-analysis. Pancreatology 2020; 20:1739-1746. [PMID: 33077384 DOI: 10.1016/j.pan.2020.10.025] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2020] [Revised: 09/17/2020] [Accepted: 10/05/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND/OBJECTIVES Consensus guidelines recommend surveillance of high-risk individuals (HRIs) for pancreatic cancer (PC) using endoscopic ultrasonography (EUS) and/or magnetic resonance imaging (MRI). This study aims to assess the yield of PC surveillance programs of HRIs and compare the detection of high-grade dysplasia or T1N0M0 adenocarcinoma by EUS and MRI. METHODS The MEDLINE and Embase (Ovid) databases were searched for prospective studies published up to April 11, 2019 using EUS and/or MRI to screen HRIs for PC. Baseline detection of focal pancreatic abnormalities, cystic lesions, solid lesions, high-grade dysplasia or T1N0M0 adenocarcinoma, and all pancreatic adenocarcinoma were recorded. Weighted pooled proportions of outcomes detected were compared between EUS and MRI using random effects modeling. RESULTS A total of 1097 studies were reviewed and 24 were included, representing 2112 HRIs who underwent imaging. The weighted pooled proportion of focal pancreatic abnormalities detected by baseline EUS (0.34, 95% CI 0.30-0.37) was significantly higher (p = 0.006) than by MRI (0.31, 95% CI 0.28-0.33). There were no significant differences between EUS and MRI in detection of other outcomes. The overall weighted pooled proportion of patients with high-grade dysplasia or T1N0M0 adenocarcinoma detected at baseline (regardless of imaging modality) was 0.0090 (95% CI 0.0022-0.016), corresponding to a number-needed-to-screen (NNS) of 111 patients to detect one high-grade dysplasia or T1N0M0 adenocarcinoma. CONCLUSIONS Surveillance programs are successful in detecting high-risk precursor lesions. No differences between EUS and MRI were noted in the detection of high-grade dysplasia or T1N0M0 adenocarcinoma, supporting the use of either imaging modality.
Collapse
Affiliation(s)
- Nina Kogekar
- Department of Medicine, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, Box 1060, New York, NY, 10029, USA
| | - Kelly E Diaz
- Department of Medicine, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, Box 1060, New York, NY, 10029, USA
| | - Alan D Weinberg
- Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY, 10029, USA
| | - Aimee L Lucas
- Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, Box 1060, New York, NY, 10029, USA.
| |
Collapse
|
|
30
|
Scholten L, Latenstein AE, Aalfs CM, Bruno MJ, Busch OR, Bonsing BA, Koerkamp BG, Molenaar IQ, Ubbink DT, van Hooft JE, Fockens P, Glas J, DeVries JH, Besselink MG. Prophylactic total pancreatectomy in individuals at high risk of pancreatic ductal adenocarcinoma (PROPAN): systematic review and shared decision-making programme using decision tables. United European Gastroenterol J 2020; 8:865-877. [PMID: 32703081 PMCID: PMC7707864 DOI: 10.1177/2050640620945534] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Background Individuals with a very high lifetime risk of developing pancreatic ductal adenocarcinoma; for example, hereditary pancreatitis and main-duct or mixed-type intraductal papillary mucinous neoplasm, may wish to discuss prophylactic total pancreatectomy but strategies to do so are lacking. Objective To develop a shared decision-making programme for prophylactic total pancreatectomy using decision tables. Methods Focus group meetings with patients were used to identify relevant questions. Systematic reviews were performed to answer these questions. Results The first tables included hereditary pancreatitis and main-duct or mixed-type intraductal papillary mucinous neoplasm. No studies focused on prophylactic total pancreatectomy in these groups. In 52 studies (3570 patients), major morbidity after total pancreatectomy was 25% and 30-day mortality was 6%. After minimally invasive total pancreatectomy (seven studies, 35 patients) this was, respectively, 13% and 0%. Exocrine insufficiency-related symptoms occurred in 33%. Quality of life after total pancreatectomy was slightly lower compared with the general population. Conclusion The decision tables can be helpful for discussing prophylactic total pancreatectomy with individuals at high risk of pancreatic ductal adenocarcinoma.
Collapse
Affiliation(s)
- Lianne Scholten
- Department of Surgery, University of Amsterdam, Amsterdam, The Netherlands.,Department of Internal Medicine, University of Amsterdam, Amsterdam, The Netherlands
| | | | - Cora M Aalfs
- Department of Clinical Genetics, University of Amsterdam, Amsterdam, The Netherlands
| | - Marco J Bruno
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Olivier R Busch
- Department of Surgery, University of Amsterdam, Amsterdam, The Netherlands
| | - Bert A Bonsing
- Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
| | - Bas Groot Koerkamp
- Department of Surgery, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - I Quintus Molenaar
- Department of Surgery, St Antonius Hospital Nieuwegein and University Medical Center Utrecht Cancer Center, Utrecht, The Netherlands
| | - Dirk T Ubbink
- Department of Surgery, University of Amsterdam, Amsterdam, The Netherlands
| | - Jeanin E van Hooft
- Department of Gastroenterology and Hepatology, University of Amsterdam, The Netherlands
| | - Paul Fockens
- Department of Gastroenterology and Hepatology, University of Amsterdam, The Netherlands
| | - Jolanda Glas
- Dutch Pancreatic Cancer Patient Organisation, 'Living with Hope', Utrecht, The Netherlands
| | - J Hans DeVries
- Department of Internal Medicine, University of Amsterdam, Amsterdam, The Netherlands
| | - Marc G Besselink
- Department of Surgery, University of Amsterdam, Amsterdam, The Netherlands
| | | |
Collapse
|
|
31
|
Use of Biomarkers and Imaging for Early Detection of Pancreatic Cancer. Cancers (Basel) 2020; 12:cancers12071965. [PMID: 32707720 PMCID: PMC7409286 DOI: 10.3390/cancers12071965] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2020] [Revised: 07/04/2020] [Accepted: 07/09/2020] [Indexed: 12/19/2022] Open
Abstract
Pancreatic cancer remains one of the deadliest cancers worldwide, and it is typically diagnosed late, with a poor prognosis. Early detection is the most important underlying factor for improving the prognosis of pancreatic cancer patients. One of the most effective strategies for detecting cancers at an early stage is screening of the general population. However, because of the low incidence of pancreatic cancer in the general population, the stratification of subjects who need to undergo further examinations by invasive and expensive modalities is important. Therefore, minimally invasive modalities involving biomarkers and imaging techniques that would facilitate the early detection of pancreatic cancer are highly needed. Multiple types of new blood biomarkers have recently been developed, including unique post-translational modifications of circulating proteins, circulating exosomes, microRNAs, and circulating tumor DNA. We previously reported that circulating apolipoprotein A2 undergoes unique processing in the bloodstream of patients with pancreatic cancer and its precancerous lesions. Additionally, we recently demonstrated a new method for measuring pancreatic proton density in the fat fraction using a fat–water magnetic resonance imaging technique that reflects pancreatic steatosis. In this review, we describe recent developments in potential biomarkers and imaging modalities for the early detection and risk stratification of pancreatic cancer, and we discuss current strategies for implementing screening programs for pancreatic cancer.
Collapse
|
|
32
|
Canto MI, Kerdsirichairat T, Yeo CJ, Hruban RH, Shin EJ, Almario JA, Blackford A, Ford M, Klein AP, Javed AA, Lennon AM, Zaheer A, Kamel IR, Fishman EK, Burkhart R, He J, Makary M, Weiss MJ, Schulick RD, Goggins MG, Wolfgang CL. Surgical Outcomes After Pancreatic Resection of Screening-Detected Lesions in Individuals at High Risk for Developing Pancreatic Cancer. J Gastrointest Surg 2020; 24:1101-1110. [PMID: 31197699 PMCID: PMC6908777 DOI: 10.1007/s11605-019-04230-z] [Citation(s) in RCA: 54] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2018] [Accepted: 04/10/2019] [Indexed: 01/31/2023]
Abstract
BACKGROUND Screening high-risk individuals (HRI) can detect potentially curable pancreatic ductal adenocarcinoma (PDAC) and its precursors. We describe the outcomes of high-risk individuals (HRI) after pancreatic resection of screen-detected neoplasms. METHODS Asymptomatic HRI enrolled in the prospective Cancer of the Pancreas Screening (CAPS) studies from 1998 to 2014 based on family history or germline mutations undergoing surveillance for at least 6 months were included. Pathologic diagnoses, hospital length of stay, incidence of diabetes mellitus, operative morbidity, need for repeat operation, and disease-specific mortality were determined. RESULTS Among 354 HRI, 48 (13.6%) had 57 operations (distal pancreatectomy (31), Whipple (20), and total pancreatectomy (6)) for suspected pancreatic neoplasms presenting as a solid mass (22), cystic lesion(s) (25), or duct stricture (1). The median length of stay was 7 days (IQR 5-11). Nine of the 42 HRI underwent completion pancreatectomy for a new lesion after a median of 3.8 years (IQR 2.5-7.6). Postoperative complications developed in 17 HRI (35%); there were no perioperative deaths. New-onset diabetes mellitus after partial resection developed in 20% of HRI. Fourteen PDACs were diagnosed, 11 were screen-detected, 10 were resectable, and 9 had an R0 resection. Metachronous PDAC developed in remnant pancreata of 2 HRI. PDAC-related mortality was 4/10 (40%), with 90% 1-year survival and 60% 5-year survival, respectively. CONCLUSIONS Screening HRI can detect PDAC with a high resectability rate. Surgical treatment is associated with a relatively short length of stay and low readmission rate, acceptable morbidity, zero 90-day mortality, and significant long-term survival. CLINICAL TRIAL REGISTRATION NUMBER NCT2000089.
Collapse
Affiliation(s)
- Marcia Irene Canto
- Departments of Medicine (Gastroenterology), The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland
| | - Tossapol Kerdsirichairat
- Departments of Medicine (Gastroenterology), The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland
| | - Charles J. Yeo
- Department of Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania
| | - Ralph H. Hruban
- Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland
| | - Eun Ji Shin
- Departments of Medicine (Gastroenterology), The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland
| | - Jose Alejandro Almario
- Departments of Medicine (Gastroenterology), The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland
| | - Amanda Blackford
- Department of Oncology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland
| | - Madeline Ford
- Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland
| | - Alison P. Klein
- Department of Oncology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland
| | - Ammar A. Javed
- Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland
| | - Anne Marie Lennon
- Departments of Medicine (Gastroenterology), The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland
| | - Atif Zaheer
- Department of Radiology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland
| | - Ihab R. Kamel
- Department of Radiology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland
| | - Elliot K. Fishman
- Department of Radiology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland
| | - Richard Burkhart
- Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland
| | - Jin He
- Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland
| | - Martin Makary
- Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland
| | - Matthew J. Weiss
- Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland
| | | | - Michael G. Goggins
- Departments of Medicine (Gastroenterology), The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland,Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland
| | - Christopher L. Wolfgang
- Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland
| |
Collapse
|
|
33
|
Abe T, Koi C, Kohi S, Song KB, Tamura K, Macgregor-Das A, Kitaoka N, Chuidian M, Ford M, Dbouk M, Borges M, He J, Burkhart R, Wolfgang CL, Klein AP, Eshleman JR, Hruban RH, Canto MI, Goggins M. Gene Variants That Affect Levels of Circulating Tumor Markers Increase Identification of Patients With Pancreatic Cancer. Clin Gastroenterol Hepatol 2020; 18:1161-1169.e5. [PMID: 31676359 PMCID: PMC7166164 DOI: 10.1016/j.cgh.2019.10.036] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2019] [Revised: 09/24/2019] [Accepted: 10/04/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Levels of carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), and cancer antigen 125 (CA-125) in blood are used as markers to determine the response of patients with cancer to therapy, but are not used to identify patients with pancreatic cancer. METHODS We obtained blood samples from 504 patients undergoing pancreatic surveillance from 2002 through 2018 who did not develop pancreatic cancer and measured levels of the tumor markers CA19-9, CEA, CA-125, and thrombospondin-2. Single-nucleotide polymorphisms (SNPs) in FUT3, FUT2, ABO, and GAL3ST2 that have been associated with levels of tumor markers were used to establish SNP-defined ranges for each tumor marker. We also tested the association between additional SNPs (in FUT6, MUC16, B3GNT3, FAM3B, and THBS2) with levels of tumor markers. To calculate the diagnostic specificity of each SNP-defined range, we assigned the patients under surveillance into training and validation sets. After determining the SNP-defined ranges, we determined the sensitivity of SNP-adjusted tests for the tumor markers, measuring levels in blood samples from 245 patients who underwent resection for pancreatic ductal adenocarcinoma (PDAC) from 2010 through 2017. RESULTS A level of CA19-9 that identified patients with PDAC with 99% specificity had 52.7% sensitivity. When we set the cut-off levels of CA19-9 based on each SNP, the test for CA19-9 identified patients with PDAC with 60.8% sensitivity and 98.8% specificity. Among patients with FUT3 alleles that encode a functional protein, levels of CA19-9 greater than the SNP-determined cut-off values identified 66.4% of patients with PDAC, with 99.3% specificity. In the validation set, levels of CEA varied among patients with vs without SNP in FUT2, by blood group, and among smokers vs nonsmokers; levels of CA-125 varied among patients with vs without the SNP in GAL3ST2. The use of the SNPs to define the ranges of CEA and CA-125 did not significantly increase the diagnostic accuracy of the assays for these proteins. Combining data on levels of CA19-9 and CEA, CA19-9 and CA-125, or CA19-9 and thrombospondin-2 increased the sensitivity of detection of PDAC, but slightly reduced specificity. CONCLUSIONS Including information on SNPs associated with levels of CA19-9, CEA, and CA-125 can improve the diagnostic accuracy of assays for these tumor markers in the identification of patients with PDAC. Clinicaltrials.gov no: NCT02000089.
Collapse
Affiliation(s)
- Toshiya Abe
- Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland
| | - Chiho Koi
- Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland
| | - Shiro Kohi
- Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland
| | - Ki-Byung Song
- Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland
| | - Koji Tamura
- Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland
| | - Anne Macgregor-Das
- Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland
| | - Naoki Kitaoka
- Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland
| | - Miguel Chuidian
- Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland
| | - Madeline Ford
- Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland
| | - Mohamad Dbouk
- Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland
| | - Michael Borges
- Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland
| | - Jin He
- Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland
| | - Richard Burkhart
- Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland
| | - Christopher L Wolfgang
- Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland
| | - Alison P Klein
- Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland; Department of Oncology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland
| | - James R Eshleman
- Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland; Department of Oncology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland
| | - Ralph H Hruban
- Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland; Department of Oncology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland
| | - Marcia Irene Canto
- Department of Oncology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland; Department of Medicine, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland
| | - Michael Goggins
- Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland; Department of Oncology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland; Department of Medicine, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland.
| |
Collapse
|
|
34
|
Abstract
OBJECTIVES Abnormalities of the main pancreatic duct may be an early indicator of pancreatic ductal adenocarcinoma (PDAC). We develop and validate algorithms that predict the risk of PDAC using features identified on cross-sectional imaging and other clinical characteristics collected through electronic medical records. METHODS Adult patients with abdominal computed tomography or magnetic resonance imaging in January 2006 to June 2016 demonstrating dilatation of main pancreatic duct were identified. Pancreas-related morphologic features were extracted from radiology reports using natural language processing. The cumulative incidence of PDAC with death as a competing risk was estimated using multistate models. Model discrimination was assessed using c-index. The models were internally validated using bootstrapping. RESULTS The cohort consisted of 7819 patients (mean age, 71 years; 65% female). A total of 781 patients (10%) developed PDAC within 3 years after the first eligible imaging study. The final models achieved reasonable discrimination (c-index, 0.825-0.833). The 3-year average risk of PDAC in the top 5% of the total eligible patients was 56.0%, more than 20 times of the average risk among the bottom 50% of patients. CONCLUSIONS Prediction models combining imaging features and clinical measures can be used to further stratify the risk of pancreatic cancer among patients with pancreas ductal dilatation.
Collapse
|
|
35
|
Matsubayashi H, Takaori K, Morizane C, Kiyozumi Y. Familial Pancreatic Cancer and Surveillance of High-Risk Individuals. Gut Liver 2020; 13:498-505. [PMID: 30917631 PMCID: PMC6743804 DOI: 10.5009/gnl18449] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2018] [Revised: 12/04/2018] [Accepted: 12/13/2018] [Indexed: 12/15/2022] Open
Abstract
Family history of pancreatic cancer (PC) is a risk factor for PC development, and the risk level correlates with the number of affected families. A case of PC with ≥1 PC cases in the first-degree relative is broadly defined as familial pancreatic cancer (FPC) and accounts for 5% to 10% of total PC cases. FPC possesses several epidemiological, genetic and clinicopathological aspects that are distinct from those of conventional PCs. In Western countries, FPC registries have been established since the 1990s, and high-risk individuals are screened to detect early PCs. For the pharmacotherapy of FPC, especially in cases with germline pathogenic BRCA mutations, regimens using platinum and poly (ADP-ribose) polymerase inhibitor have recently been studied for their effectiveness. To date, the concept of FPC has prevailed in Western countries, and it has begun to infiltrate into Eastern countries. As the genetic background and environmental conditions vary in association with ethnicity and living area, we need to establish our own FPC registries and accumulate data in Asian countries.
Collapse
Affiliation(s)
- Hiroyuki Matsubayashi
- Divisions of Genetic Medicine Promotion, Shizuoka Cancer Center, Shizuoka, Japan.,Divisions of Endoscopy, Shizuoka Cancer Center, Shizuoka, Japan
| | - Kyoichi Takaori
- Department of Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Chigusa Morizane
- Division of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Yoshimi Kiyozumi
- Divisions of Genetic Medicine Promotion, Shizuoka Cancer Center, Shizuoka, Japan
| |
Collapse
|
|
36
|
Goggins M, Overbeek KA, Brand R, Syngal S, Del Chiaro M, Bartsch DK, Bassi C, Carrato A, Farrell J, Fishman EK, Fockens P, Gress TM, van Hooft JE, Hruban RH, Kastrinos F, Klein A, Lennon AM, Lucas A, Park W, Rustgi A, Simeone D, Stoffel E, Vasen HFA, Cahen DL, Canto MI, Bruno M. Management of patients with increased risk for familial pancreatic cancer: updated recommendations from the International Cancer of the Pancreas Screening (CAPS) Consortium. Gut 2020; 69:7-17. [PMID: 31672839 PMCID: PMC7295005 DOI: 10.1136/gutjnl-2019-319352] [Citation(s) in RCA: 365] [Impact Index Per Article: 73.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2019] [Revised: 09/05/2019] [Accepted: 09/28/2019] [Indexed: 12/14/2022]
Abstract
BACKGROUND AND AIM The International Cancer of the Pancreas Screening Consortium met in 2018 to update its consensus recommendations for the management of individuals with increased risk of pancreatic cancer based on family history or germline mutation status (high-risk individuals). METHODS A modified Delphi approach was employed to reach consensus among a multidisciplinary group of experts who voted on consensus statements. Consensus was considered reached if ≥75% agreed or disagreed. RESULTS Consensus was reached on 55 statements. The main goals of surveillance (to identify high-grade dysplastic precursor lesions and T1N0M0 pancreatic cancer) remained unchanged. Experts agreed that for those with familial risk, surveillance should start no earlier than age 50 or 10 years earlier than the youngest relative with pancreatic cancer, but were split on whether to start at age 50 or 55. Germline ATM mutation carriers with one affected first-degree relative are now considered eligible for surveillance. Experts agreed that preferred surveillance tests are endoscopic ultrasound and MRI/magnetic retrograde cholangiopancreatography, but no consensus was reached on how to alternate these modalities. Annual surveillance is recommended in the absence of concerning lesions. Main areas of disagreement included if and how surveillance should be performed for hereditary pancreatitis, and the management of indeterminate lesions. CONCLUSIONS Pancreatic surveillance is recommended for selected high-risk individuals to detect early pancreatic cancer and its high-grade precursors, but should be performed in a research setting by multidisciplinary teams in centres with appropriate expertise. Until more evidence supporting these recommendations is available, the benefits, risks and costs of surveillance of pancreatic surveillance need additional evaluation.
Collapse
Affiliation(s)
- Michael Goggins
- Pathology, Medicine Oncology, Johns Hopkins University, Baltimore, Maryland, USA
| | | | - Randall Brand
- Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Sapna Syngal
- GI Cancer Genetics and Prevention Program, Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts, USA
| | - Marco Del Chiaro
- Department of Surgery, Division of Surgical Oncology, Denver, Colorado, USA
| | - Detlef K Bartsch
- Division of Visceral, Thoracic and Vascular Surgery, University of Marburg, Marburg, Germany
| | - Claudio Bassi
- Department of Surgey, University of Verona, Verona, Italy
| | | | - James Farrell
- Medicine, Yale University School of Medicine, New Haven, Connecticut, USA
| | - Elliot K Fishman
- The Russell H Morgan Department of Radiology and Radiological Science, Baltimore, Maryland, USA
| | - Paul Fockens
- Department of Gastroenterology & Hepatology, Amsterdam Gastroenterology & Metabolism, Amsterdam, The Netherlands
| | - Thomas M Gress
- Gastroenterology, Endocrinology, Metabolism and Infectiology, University of Marburg, Marburg, Germany
| | - Jeanin E van Hooft
- Gastroenterology and Hepatology, Amsterdam University Medical Centres, Amsterdam, The Netherlands
| | - R H Hruban
- Department of Pathology, Johns Hopkins University, Baltimore, Maryland, USA
| | - Fay Kastrinos
- Division of Digestive and Liver Diseases, Columbia University Medical Center, New York City, New York, USA,Division of Digestive and Liver Diseases, Columbia University, New York City, New York, USA
| | - Allison Klein
- Oncology, Johns Hopkins University, Baltimore, Maryland, USA
| | | | - Aimee Lucas
- Gastroenterology, Icahn School of Medicine at Mount Sinai, New York City, New York, USA
| | - Walter Park
- Division of Digestive and Liver Diseases, Columbia University Medical Center, New York City, New York, USA
| | - Anil Rustgi
- Division of Digestive and Liver Diseases, Columbia University, New York City, New York, USA
| | - Diane Simeone
- New York University Medical Center, New York City, New York, USA
| | | | - Hans F A Vasen
- Gastroenterology and Hepatology, Leiden University, Leiden, The Netherlands
| | - Djuna L Cahen
- Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands
| | | | - Marco Bruno
- Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands
| | | |
Collapse
|
|
37
|
Lennon KM, Wakefield DL, Maddox AL, Brehove MS, Willner AN, Garcia-Mansfield K, Meechoovet B, Reiman R, Hutchins E, Miller MM, Goel A, Pirrotte P, Van Keuren-Jensen K, Jovanovic-Talisman T. Single molecule characterization of individual extracellular vesicles from pancreatic cancer. J Extracell Vesicles 2019; 8:1685634. [PMID: 31741725 PMCID: PMC6844376 DOI: 10.1080/20013078.2019.1685634] [Citation(s) in RCA: 65] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2019] [Revised: 08/30/2019] [Accepted: 10/21/2019] [Indexed: 12/19/2022] Open
Abstract
Biofluid-accessible extracellular vesicles (EVs) may represent a new means to improve the sensitivity and specificity of detecting disease. However, current methods to isolate EVs encounter challenges when they are used to select specific populations. Moreover, it has been difficult to comprehensively characterize heterogeneous EV populations at the single vesicle level. Here, we robustly assessed heterogeneous EV populations from cultured cell lines via nanoparticle tracking analysis, proteomics, transcriptomics, transmission electron microscopy, and quantitative single molecule localization microscopy (qSMLM). Using qSMLM, we quantified the size and biomarker content of individual EVs. We applied qSMLM to patient plasma samples and identified a pancreatic cancer-enriched EV population. Our goal is to advance single molecule characterization of EVs for early disease detection. Abbreviations: EV: Extracellular Vesicle; qSMLM: quantitative Single Molecule Localization Microscopy; PDAC: Pancreatic Ductal Adenocarcinoma; EGFR: epidermal growth factor receptor 1; CA19-9: carbohydrate antigen 19-9; SEC: size exclusion chromatography; WGA: wheat germ agglutinin; AF647: Alexa Fluor 647; Ab: antibody; HPDEC: Healthy Pancreatic Ductal Epithelial Cell; TEM: Transmission Electron Microscopy.
Collapse
Affiliation(s)
- Kathleen M Lennon
- Department of Molecular Medicine, Beckman Research Institute of the City of Hope Comprehensive Cancer Center, Duarte, CA, USA
| | - Devin L Wakefield
- Department of Molecular Medicine, Beckman Research Institute of the City of Hope Comprehensive Cancer Center, Duarte, CA, USA
| | - Adam L Maddox
- Department of Molecular Medicine, Beckman Research Institute of the City of Hope Comprehensive Cancer Center, Duarte, CA, USA
| | - Matthew S Brehove
- Department of Molecular Medicine, Beckman Research Institute of the City of Hope Comprehensive Cancer Center, Duarte, CA, USA
| | - Ari N Willner
- Department of Molecular Medicine, Beckman Research Institute of the City of Hope Comprehensive Cancer Center, Duarte, CA, USA
| | - Krystine Garcia-Mansfield
- Collaborative Center for Translational Mass Spectrometry, Translational Genomics Research Institute, Phoenix, AZ, USA
| | - Bessie Meechoovet
- Neurogenomics Division, Center for Noninvasive Diagnostics, Translational Genomics Research Institute, Phoenix, AZ, USA
| | - Rebecca Reiman
- Neurogenomics Division, Center for Noninvasive Diagnostics, Translational Genomics Research Institute, Phoenix, AZ, USA
| | - Elizabeth Hutchins
- Neurogenomics Division, Center for Noninvasive Diagnostics, Translational Genomics Research Institute, Phoenix, AZ, USA
| | - Marcia M Miller
- Department of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute of the City of Hope Comprehensive Cancer Center, Duarte, CA, USA
| | - Ajay Goel
- Center for Gastrointestinal Research, Center for Translational Genomics and Oncology, Baylor Scott & White Research Institute and Charles A. Sammons Cancer Center, Baylor University Medical Center, Dallas, TX, USA
| | - Patrick Pirrotte
- Collaborative Center for Translational Mass Spectrometry, Translational Genomics Research Institute, Phoenix, AZ, USA
| | - Kendall Van Keuren-Jensen
- Neurogenomics Division, Center for Noninvasive Diagnostics, Translational Genomics Research Institute, Phoenix, AZ, USA.,Department of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute of the City of Hope Comprehensive Cancer Center, Duarte, CA, USA
| | - Tijana Jovanovic-Talisman
- Department of Molecular Medicine, Beckman Research Institute of the City of Hope Comprehensive Cancer Center, Duarte, CA, USA
| |
Collapse
|
|
38
|
Matsubayashi H, Kiyozumi Y, Ishiwatari H, Uesaka K, Kikuyama M, Ono H. Surveillance of Individuals with a Family History of Pancreatic Cancer and Inherited Cancer Syndromes: A Strategy for Detecting Early Pancreatic Cancers. Diagnostics (Basel) 2019; 9:E169. [PMID: 31683730 PMCID: PMC6963266 DOI: 10.3390/diagnostics9040169] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2019] [Revised: 10/29/2019] [Accepted: 10/30/2019] [Indexed: 12/13/2022] Open
Abstract
A family history of pancreatic cancer (PC) is a risk factor of PC, and risk levels increase as affected families grow in number and/or develop PC at younger ages. Familial pancreatic cancer (FPC) is defined as a client having at least two PC cases in a first degree relatives. In the narrow sense, FPC does not include some inherited cancer syndromes that are known to increase the risks of PC, such as Peutz-Jeghers syndrome (PJS), hereditary pancreatitis (HP), hereditary breast ovarian cancer syndrome (HBOC), and so on. FPC accounts for 5%-10% of total PC diagnoses and is marked by several features in genetic, epidemiological, and clinicopathological findings that are similar to or distinct from conventional PC. Recent advances in genetic medicine have led to an increased ability to identify germline variants of cancer-associated genes. To date, high-risk individuals (HRIs) in many developed countries, including FPC kindreds and inherited cancer syndromes, are screened clinically to detect and treat early-stage PC. This article highlights the concept of FPC and the most recent data on its detection.
Collapse
Affiliation(s)
- Hiroyuki Matsubayashi
- Division of Endoscopy, Shizuoka Cancer Center, Shizuoka 411-8777, Japan.
- Division of Genetic Medicine Promotion, Shizuoka Cancer Center, Shizuoka 411-8777, Japan.
| | - Yoshimi Kiyozumi
- Division of Genetic Medicine Promotion, Shizuoka Cancer Center, Shizuoka 411-8777, Japan.
| | | | - Katsuhiko Uesaka
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Shizuoka 411-8777, Japan.
| | - Masataka Kikuyama
- Department of Gastroenterology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo 113-0021, Japan.
| | - Hiroyuki Ono
- Division of Endoscopy, Shizuoka Cancer Center, Shizuoka 411-8777, Japan.
| |
Collapse
|
|
39
|
Lorenzo D, Rebours V, Maire F, Palazzo M, Gonzalez JM, Vullierme MP, Aubert A, Hammel P, Lévy P, Mestier LD. Role of endoscopic ultrasound in the screening and follow-up of high-risk individuals for familial pancreatic cancer. World J Gastroenterol 2019; 25:5082-5096. [PMID: 31558858 PMCID: PMC6747297 DOI: 10.3748/wjg.v25.i34.5082] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2019] [Revised: 08/04/2019] [Accepted: 08/24/2019] [Indexed: 02/06/2023] Open
Abstract
Managing familial pancreatic cancer (FPC) is challenging for gastroenterologists, surgeons and oncologists. High-risk individuals (HRI) for pancreatic cancer (PC) (FPC or with germline mutations) are a heterogeneous group of subjects with a theoretical lifetime cumulative risk of PC over 5%. Screening is mainly based on annual magnetic resonance imaging (MRI) and endoscopic ultrasound (EUS). The goal of screening is to identify early-stage operable cancers or high-risk precancerous lesions (pancreatic intraepithelial neoplasia or intraductal papillary mucinous neoplasms with high-grade dysplasia). In the literature, target lesions are identified in 2%-5% of HRI who undergo screening. EUS appears to provide better identification of small solid lesions (0%-46% of HRI) and chronic-pancreatitis-like parenchymal changes (14%-77% of HRI), while MRI is probably the best modality to identify small cystic lesions (13%-49% of HRI). There are no specific studies in HRI on the use of contrast-enhanced harmonic EUS. EUS can also be used to obtain tissue samples. Nevertheless, there is still limited evidence on the accuracy of imaging procedures used for screening or agreement on which patients to treat. The cost-effectiveness of screening is also unclear. Certain new EUS-related techniques, such as searching for DNA abnormalities or protein markers in pancreatic fluid, appear to be promising.
Collapse
Affiliation(s)
- Diane Lorenzo
- Pancreatology Department, Beaujon Hospital, Assistance Publique-Hôpitaux de Paris, Clichy, and Paris Diderot University, Paris 75013, France
| | - Vinciane Rebours
- Pancreatology Department, Beaujon Hospital, Assistance Publique-Hôpitaux de Paris, Clichy, and Paris Diderot University, Paris 75013, France
- INSERM, UMR1149, Paris 92110, France
| | - Frédérique Maire
- Pancreatology Department, Beaujon Hospital, Assistance Publique-Hôpitaux de Paris, Clichy, and Paris Diderot University, Paris 75013, France
| | - Maxime Palazzo
- Pancreatology Department, Beaujon Hospital, Assistance Publique-Hôpitaux de Paris, Clichy, and Paris Diderot University, Paris 75013, France
| | - Jean-Michel Gonzalez
- Departement of Gastroenterology, Aix Marseille university - APHM - Hôpital Nord, Marseille 13000, France
| | - Marie-Pierre Vullierme
- Radiology Department, Beaujon Hospital, Assistance Publique-Hôpitaux de Paris, Clichy, and Paris Diderot University, Paris 92110, France
| | - Alain Aubert
- Pancreatology Department, Beaujon Hospital, Assistance Publique-Hôpitaux de Paris, Clichy, and Paris Diderot University, Paris 75013, France
| | - Pascal Hammel
- Oncology Department, Beaujon Hospital, Assistance Publique-Hôpitaux de Paris, Clichy, and Paris Diderot University, Paris 92110, France
| | - Philippe Lévy
- Pancreatology Department, Beaujon Hospital, Assistance Publique-Hôpitaux de Paris, Clichy, and Paris Diderot University, Paris 75013, France
| | - Louis de Mestier
- Pancreatology Department, Beaujon Hospital, Assistance Publique-Hôpitaux de Paris, Clichy, and Paris Diderot University, Paris 75013, France
- INSERM, UMR1149, Paris 92110, France
| |
Collapse
|
|
40
|
Henrikson NB, Aiello Bowles EJ, Blasi PR, Morrison CC, Nguyen M, Pillarisetty VG, Lin JS. Screening for Pancreatic Cancer: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force. JAMA 2019; 322:445-454. [PMID: 31386140 DOI: 10.1001/jama.2019.6190] [Citation(s) in RCA: 80] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
IMPORTANCE Pancreatic adenocarcinoma is the third most common cause of cancer death among men and women in the United States. OBJECTIVE To systematically review benefits and harms of screening for pancreatic adenocarcinoma to inform the US Preventive Services Task Force. DATA SOURCES MEDLINE, PubMed, and the Cochrane Collaboration Registry of Controlled Trials, from January 2002 through April 27, 2018; surveillance through March 22, 2019. STUDY SELECTION Studies of adults with or without risk factors for pancreatic adenocarcinoma (eg, family history of pancreatic cancer, personal history of new-onset diabetes) undergoing imaging-based screening; studies of treatment for adults with screen-detected or asymptomatic pancreatic adenocarcinoma. Included study designs were randomized clinical trials, nonrandomized controlled intervention studies, diagnostic accuracy studies with a reference standard, cohort studies, and case-control studies (for evaluation of harms only). Studies consisting entirely of populations with known genetic syndromes associated with pancreatic cancer were excluded. DATA EXTRACTION AND SYNTHESIS Two investigators independently reviewed abstracts and full-text articles and rated included studies for quality; data were quantitatively analyzed to calculate a pooled diagnostic yield and narratively synthesized. MAIN OUTCOMES AND MEASURES Mortality, morbidity, or quality of life; diagnostic accuracy of screening tests; any harm of screening or treatment. RESULTS Thirteen fair-quality prospective cohort screening studies (N = 1317) conducted predominantly in populations at high familial risk for pancreatic adenocarcinoma were included. No studies reported on the effect of screening on morbidity or mortality or on the effectiveness of treatment for screen-detected pancreatic adenocarcinoma. Although no studies evaluated the diagnostic accuracy of screening tests, all 13 studies reported the diagnostic yield. Yields ranged from 0 to 75 cases per 1000 persons in studies using endoscopic ultrasound, magnetic resonance imaging, and/or computed tomography-based screening. In total, 18 cases of pancreatic adenocarcinoma were detected in 1156 adults at increased familial risk and 0 cases were detected in 161 average-risk adults. In 8 studies (n = 675) assessing procedural harms of screening, no serious harms from initial screening were reported. Two studies (n = 271) found no evidence of psychosocial harms related to screening. Evidence of surgical harms was limited. CONCLUSIONS AND RELEVANCE Imaging-based screening in groups at high familial risk can detect pancreatic adenocarcinoma with limited evidence of minimal harms. However, the effect of screening on morbidity and mortality in groups at high familial risk has not been studied, and no data are available in average-risk populations. There is limited evidence to assess benefits or harms of surgical intervention for screen-detected pancreatic adenocarcinoma.
Collapse
Affiliation(s)
- Nora B Henrikson
- Kaiser Permanente Washington Health Research Institute, Kaiser Permanente Research Affiliates Evidence-based Practice Center, Seattle
| | - Erin J Aiello Bowles
- Kaiser Permanente Washington Health Research Institute, Kaiser Permanente Research Affiliates Evidence-based Practice Center, Seattle
| | - Paula R Blasi
- Kaiser Permanente Washington Health Research Institute, Kaiser Permanente Research Affiliates Evidence-based Practice Center, Seattle
| | - Caitlin C Morrison
- Kaiser Permanente Washington Health Research Institute, Kaiser Permanente Research Affiliates Evidence-based Practice Center, Seattle
| | - Matt Nguyen
- Kaiser Permanente Washington Health Research Institute, Kaiser Permanente Research Affiliates Evidence-based Practice Center, Seattle
| | - Venu G Pillarisetty
- Hepatopancreatobiliary Service, Department of Surgery, University of Washington, Seattle
| | - Jennifer S Lin
- Kaiser Permanente Center for Health Research, Kaiser Permanente Research Affiliates Evidence-based Practice Center, Portland, Oregon
| |
Collapse
|
|
41
|
Owens DK, Davidson KW, Krist AH, Barry MJ, Cabana M, Caughey AB, Curry SJ, Doubeni CA, Epling JW, Kubik M, Landefeld CS, Mangione CM, Pbert L, Silverstein M, Simon MA, Tseng CW, Wong JB. Screening for Pancreatic Cancer: US Preventive Services Task Force Reaffirmation Recommendation Statement. JAMA 2019; 322:438-444. [PMID: 31386141 DOI: 10.1001/jama.2019.10232] [Citation(s) in RCA: 226] [Impact Index Per Article: 37.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
IMPORTANCE Pancreatic cancer is an uncommon cancer with an age-adjusted annual incidence of 12.9 cases per 100 000 person-years. However, the death rate is 11.0 deaths per 100 000 person-years because the prognosis of pancreatic cancer is poor. Although its incidence is low, pancreatic cancer is the third most common cause of cancer death in the United States. Because of the increasing incidence of pancreatic cancer, along with improvements in early detection and treatment of other types of cancer, it is estimated that pancreatic cancer may soon become the second-leading cause of cancer death in the United States. OBJECTIVE To update the 2004 US Preventive Services Task Force (USPSTF) recommendation on screening for pancreatic cancer. EVIDENCE REVIEW The USPSTF reviewed the evidence on the benefits and harms of screening for pancreatic cancer, the diagnostic accuracy of screening tests for pancreatic cancer, and the benefits and harms of treatment of screen-detected or asymptomatic pancreatic cancer. FINDINGS The USPSTF found no evidence that screening for pancreatic cancer or treatment of screen-detected pancreatic cancer improves disease-specific morbidity or mortality, or all-cause mortality. The USPSTF found adequate evidence that the magnitude of the benefits of screening for pancreatic cancer in asymptomatic adults can be bounded as no greater than small. The USPSTF found adequate evidence that the magnitude of the harms of screening for pancreatic cancer and treatment of screen-detected pancreatic cancer can be bounded as at least moderate. The USPSTF reaffirms its previous conclusion that the potential benefits of screening for pancreatic cancer in asymptomatic adults do not outweigh the potential harms. CONCLUSIONS AND RECOMMENDATION The USPSTF recommends against screening for pancreatic cancer in asymptomatic adults. (D recommendation).
Collapse
Affiliation(s)
| | - Douglas K Owens
- Veterans Affairs Palo Alto Health Care System, Palo Alto, California
- Stanford University, Stanford, California
| | - Karina W Davidson
- Feinstein Institute for Medical Research at Northwell Health, Manhasset, New York
| | - Alex H Krist
- Fairfax Family Practice Residency, Fairfax, Virginia
- Virginia Commonwealth University, Richmond
| | | | | | | | | | | | | | | | | | | | - Lori Pbert
- University of Massachusetts Medical School, Worcester
| | | | | | - Chien-Wen Tseng
- University of Hawaii, Honolulu
- Pacific Health Research and Education Institute, Honolulu, Hawaii
| | - John B Wong
- Tufts University School of Medicine, Boston, Massachusetts
| |
Collapse
|
|
42
|
Saldia A, Olson SH, Nunes P, Liang X, Samson ML, Salo-Mullen E, Marcell V, Stadler ZK, Allen PJ, Offit K, Kurtz RC. Outcome of Pancreatic Cancer Surveillance Among High-Risk Individuals Tested for Germline Mutations in BRCA1 and BRCA2. Cancer Prev Res (Phila) 2019; 12:599-608. [PMID: 31337648 DOI: 10.1158/1940-6207.capr-18-0272] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2018] [Revised: 01/22/2019] [Accepted: 07/17/2019] [Indexed: 01/07/2023]
Abstract
Germline mutations in BRCA1/2 are risk factors for pancreatic ductal adenocarcinoma (PDAC). The aim of this study was to evaluate whether results of surveillance for PDAC in high risk individuals (HRI) differ between those with and without a pathogenic BRCA1/2 mutation. This prospective study was conducted within the Pancreatic Tumor Registry at a major cancer center. There were 83 HRIs with ≥1 first-degree relative with PDAC who underwent surveillance and testing for pathogenic germline mutations in BRCA1/2 A secondary analysis includes 18 HRIs with known mutations in BRCA1/2 but with weaker family history. HRIs were evaluated over time using magnetic resonance cholangiopancreatography (MRCP) and endoscopic ultrasound when indicated by MRCP findings. We reviewed imaging results, blinded to mutation status. Demographic information was obtained from interviewer-administered questionnaires. The outcome was the proportion with any pancreatic abnormality identified at initial or follow-up surveillance. Among the 83 HRIs in the main analysis, 48 had a mutation in BRCA1/2 and 35 did not. Overall, 16 of 48 (33%) BRCA1/2-positive and 13 of 35 (37%) BRCA1/2-negative participants had pancreatic abnormalities on imaging; in each group, all but one finding was an intraductal papillary mucinous neoplasm. Among those with pathogenic mutations but weaker family history, results were similar: 7 of 18 (39%) with pancreatic abnormalities. Results of surveillance for pancreatic abnormalities on imaging are similar regardless of BRCA1/2 mutation status. While the results from this small study need confirmation in other studies, at present there does not appear to be increased yield from targeting individuals with BRCA1/2 mutations for surveillance.
Collapse
Affiliation(s)
- Amethyst Saldia
- Department of Epidemiology & Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York.
| | - Sara H Olson
- Department of Epidemiology & Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Pamela Nunes
- Department of Epidemiology & Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Xiaolin Liang
- Department of Epidemiology & Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Marguerite L Samson
- Department of Epidemiology & Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Erin Salo-Mullen
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Vanessa Marcell
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Zsofia K Stadler
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Peter J Allen
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York.,Department of Surgery, Duke University, Durham, North Carolina
| | - Kenneth Offit
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Robert C Kurtz
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
| |
Collapse
|
|
43
|
Konings ICAW, Canto MI, Almario JA, Harinck F, Saxena P, Lucas AL, Kastrinos F, Whitcomb DC, Brand RE, Lachter J, Malleo G, Paiella S, Syngal S, Saltzman JR, Stoffel EM, van Hooft JE, Hruban RH, Poley JW, Fockens P, Goggins MG, Bruno MJ. Surveillance for pancreatic cancer in high-risk individuals. BJS Open 2019; 3:656-665. [PMID: 31592073 PMCID: PMC6773633 DOI: 10.1002/bjs5.50180] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2018] [Accepted: 04/02/2019] [Indexed: 12/26/2022] Open
Abstract
Background Surveillance of individuals at high risk of pancreatic ductal adenocarcinoma (PDAC) and its precursors might lead to better outcomes. The aim of this study was to determine the prevalence and outcomes of PDAC and high-risk neoplastic precursor lesions among such patients participating in surveillance programmes. Methods A multicentre study was conducted through the International CAncer of the Pancreas Screening (CAPS) Consortium Registry to identify high-risk individuals who had undergone pancreatic resection or progressed to advanced PDAC while under surveillance. High-risk neoplastic precursor lesions were defined as: pancreatic intraepithelial neoplasia (PanIN) 3, intraductal papillary mucinous neoplasia (IPMN) with high-grade dysplasia, and pancreatic neuroendocrine tumours at least 2 cm in diameter. Results Of 76 high-risk individuals identified in 11 surveillance programmes, 71 had undergone surgery and five had been diagnosed with inoperable PDAC. Of the 71 patients who underwent resection, 32 (45 per cent) had PDAC or a high-risk precursor (19 PDAC, 4 main-duct IPMN, 4 branch-duct IPMN, 5 PanIN-3); the other 39 patients had lesions thought to be associated with a lower risk of neoplastic progression. Age at least 65 years, female sex, carriage of a gene mutation and location of a lesion in the head/uncinate region were associated with high-risk precursor lesions or PDAC. The survival of high-risk individuals with low-risk neoplastic lesions did not differ from that in those with high-risk precursor lesions. Survival was worse among patients with PDAC. There was no surgery-related mortality. Conclusion A high proportion of high-risk individuals who had surgical resection for screening- or surveillance-detected pancreatic lesions had a high-risk neoplastic precursor lesion or PDAC at the time of surgery. Survival was better in high-risk individuals who had either low- or high-risk neoplastic precursor lesions compared with that in patients who developed PDAC.
Collapse
Affiliation(s)
- I C A W Konings
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, the Netherlands
| | - M I Canto
- Department of Gastroenterology and Hepatology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
| | - J A Almario
- Department of Gastroenterology and Hepatology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
| | - F Harinck
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, the Netherlands
| | - P Saxena
- Department of Gastroenterology and Hepatology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.,Department of Gastroenterology and Hepatology, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia
| | - A L Lucas
- Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, USA
| | - F Kastrinos
- Division of Digestive and Liver Diseases, Columbia University Medical Center, New York, USA
| | - D C Whitcomb
- Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
| | - R E Brand
- Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
| | - J Lachter
- Department of Gastroenterology, Rambam Healthcare Campus, Haifa, Israel
| | - G Malleo
- Department of General Surgery, University Hospital of Verona, Verona, Italy
| | - S Paiella
- Department of General Surgery, University Hospital of Verona, Verona, Italy
| | - S Syngal
- Department of Gastroenterology, Brigham and Women's Hospital and Population Sciences Division, Dana Farber Cancer Institute, Boston, Massachusetts, USA
| | - J R Saltzman
- Department of Gastroenterology, Brigham and Women's Hospital and Population Sciences Division, Dana Farber Cancer Institute, Boston, Massachusetts, USA
| | - E M Stoffel
- Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
| | - J E van Hooft
- Department of Gastroenterology and Hepatology, Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands
| | - R H Hruban
- Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland
| | - J W Poley
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, the Netherlands
| | - P Fockens
- Department of Gastroenterology and Hepatology, Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands
| | - M G Goggins
- Department of Gastroenterology and Hepatology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
| | - M J Bruno
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, the Netherlands
| | | |
Collapse
|
|
44
|
Srivastava S, Koay EJ, Borowsky AD, De Marzo AM, Ghosh S, Wagner PD, Kramer BS. Cancer overdiagnosis: a biological challenge and clinical dilemma. Nat Rev Cancer 2019; 19:349-358. [PMID: 31024081 PMCID: PMC8819710 DOI: 10.1038/s41568-019-0142-8] [Citation(s) in RCA: 200] [Impact Index Per Article: 33.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
For cancer screening to be successful, it should primarily detect cancers with lethal potential or their precursors early, leading to therapy that reduces mortality and morbidity. Screening programmes have been successful for colon and cervical cancers, where subsequent surgical removal of precursor lesions has resulted in a reduction in cancer incidence and mortality. However, many types of cancer exhibit a range of heterogeneous behaviours and variable likelihoods of progression and death. Consequently, screening for some cancers may have minimal impact on mortality and may do more harm than good. Since the implementation of screening tests for certain cancers (for example, breast and prostate cancers), a spike in incidence of in situ and early-stage cancers has been observed, but a link to reduction in cancer-specific mortality has not been as clear. It is difficult to determine how many of these mortality reductions are due to screening and how many are due to improved treatments of tumours. In cancers with lower incidence but high mortality (for example, pancreatic cancer), screening has focused on high-risk populations, but challenges similar to those for general population screening remain, particularly with regard to finding lesions with difficult-to-characterize malignant potential (for example, intraductal papillary mucinous neoplasms). More sensitive screening methods are detecting smaller and smaller lesions, but this has not been accompanied by a comparable reduction in the incidence of invasive cancers. In this Opinion article, we focus on the contribution of screening in general and high-risk populations to overdiagnosis, the effects of overdiagnosis on patients and emerging strategies to reduce overdiagnosis of indolent cancers through an understanding of tumour heterogeneity, the biology of how cancers evolve and progress, the molecular and cellular features of early neoplasia and the dynamics of the interactions of early lesions with their surrounding tissue microenvironment.
Collapse
Affiliation(s)
- Sudhir Srivastava
- Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
| | - Eugene J Koay
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Alexander D Borowsky
- Department of Pathology and Laboratory Medicine, University of California Davis Health, Sacramento, CA, USA
| | - Angelo M De Marzo
- Department of Pathology, Johns Hopkins University, Baltimore, MD, USA
| | - Sharmistha Ghosh
- Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Paul D Wagner
- Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Barnett S Kramer
- Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| |
Collapse
|
|
45
|
Thiruvengadam SS, Chuang J, Huang R, Girotra M, Park WG. Chronic pancreatitis changes in high-risk individuals for pancreatic ductal adenocarcinoma. Gastrointest Endosc 2019; 89:842-851.e1. [PMID: 30145314 PMCID: PMC6589432 DOI: 10.1016/j.gie.2018.08.029] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2018] [Accepted: 08/13/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIMS Pancreatic intraepithelial neoplasia is associated with chronic pancreatitis (CP) changes on EUS. The objective of this study was to determine whether CP changes were more common in high-risk individuals (HRIs) than in control subjects and whether these changes differed among higher-risk subsets of HRIs. METHODS HRIs and control subjects were identified from an endoscopy database. HRIs were defined as having predisposing mutations or a family history (FH) of pancreatic ductal adenocarcinoma. HRIs were classified as vHRIs who met Cancer of the Pancreas Screening (CAPS) criteria for high risk and mHRIs who did not. Multivariable logistic regression was used to adjust for confounders and CP risk factors. RESULTS Sixty-five HRIs (44 vHRIs, 21 mHRIs) and 118 control subjects were included. HRIs were included for FH (25), Lynch syndrome (5), Peutz-Jeghers syndrome (2), and mutations in BRCA1/2 (26), PALB2 (3), ATM (3), and CDKN2A (1). After adjustment for relevant variables, HRIs were 16 times more likely to exhibit 3 or more CP changes than control subjects (95% confidence interval, 2.6-97.0; P = .003). HRIs were also more likely to have hypoechoic foci (odds ratio, 8.0; 95% confidence interval, 1.9-32.9; P = .004). vHRIs and mHRIs did not differ in frequency of 3 or more CP changes on EUS. CONCLUSIONS HRIs were more likely to exhibit CP changes and hypoechoic foci on EUS compared with control subjects. HRIs with these findings may require closer surveillance. HRIs who did or did not meet CAPS criteria did not differ with regard to CP findings, supporting a more inclusive approach to screening.
Collapse
Affiliation(s)
| | - Judith Chuang
- Department of Gastroenterology and Hepatology, Stanford Hospital and Clinics, Stanford, California, USA
| | - Robert Huang
- Department of Gastroenterology and Hepatology, Stanford Hospital and Clinics, Stanford, California, USA
| | - Mohit Girotra
- Department of Gastroenterology and Hepatology, University of Miami Hospitals and Clinics, Miami, Florida, USA
| | - Walter G. Park
- Department of Gastroenterology and Hepatology, Stanford Hospital and Clinics, Stanford, California, USA
| |
Collapse
|
|
46
|
Lucien F, Lac V, Billadeau DD, Borgida A, Gallinger S, Leong HS. Glypican-1 and glycoprotein 2 bearing extracellular vesicles do not discern pancreatic cancer from benign pancreatic diseases. Oncotarget 2019; 10:1045-1055. [PMID: 30800217 PMCID: PMC6383691 DOI: 10.18632/oncotarget.26620] [Citation(s) in RCA: 38] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2018] [Accepted: 01/09/2019] [Indexed: 01/05/2023] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease that is clinically asymptomatic in its early stages of development. Non-invasive testing for pancreatic cancer biomarkers would significantly improve early detection and patient care. Extracellular vesicles (EVs) are circulating tumor fragments present in the blood and may express cancer specific biomarkers that would enable early detection of pancreatic cancer. We tested the utility of a blood test enumerating EVs positive for the pancreas-specific marker Glycoprotein 2 (GP2) and the putative pancreatic cancer marker Glypican-1 (GPC1) in patients with PDAC. Various levels of GPC1-positive and GP2/GPC1-positive EVs were detected in PDAC patients but were not significantly higher than benign pancreatic disease (BPD) patients. The sensitivity and specificity of the GPC1 EV test was 26.67% and 87.50% respectively, whereas the sensitivity and specificity for the GPC1+GP2 EV test was 23.33% and 90.00% respectively. Immunohistochemistry of GPC1 expression in a tissue microarray of PDAC and various controls also did not demonstrate specificity of GPC1 to PDAC. Hence, enumeration of GPC1-positive EVs, solely or in conjunction with GP2, was unable to effectively distinguish between BPD and pancreatic cancer.
Collapse
Affiliation(s)
| | - Vivian Lac
- Department of Pathology and Laboratory Medicine, Western University, London, ON, Canada
| | | | - Ayelet Borgida
- Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Toronto, ON, Canada
| | - Steven Gallinger
- Department of Surgery, University Health Network, Toronto, ON, Canada
| | - Hon S Leong
- Department of Urology, Mayo Clinic, Rochester, MN, USA.,Department of Pathology and Laboratory Medicine, Western University, London, ON, Canada
| |
Collapse
|
|
47
|
Corrias G, Raeside MC, Agostini A, Huicochea-Castellanos S, Aramburu-Nunez D, Paudyal R, Shukla-Dave A, Smelianskaia O, Capanu M, Zheng J, Fung M, Kelsen DP, Mangino DA, Robson ME, Goldfrank DJ, Carter J, Allen PJ, Conti B, Monti S, Do RKG, Mannelli L. Pilot study of rapid MR pancreas screening for patients with BRCA mutation. Eur Radiol 2019; 29:3976-3985. [PMID: 30689033 DOI: 10.1007/s00330-018-5975-0] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2018] [Revised: 10/16/2018] [Accepted: 12/14/2018] [Indexed: 01/03/2023]
Abstract
PURPOSE To develop and optimize a rapid magnetic resonance imaging (MRI) screening protocol for pancreatic cancer to be performed in conjunction with breast MRI screening in breast cancer susceptibility gene (BRCA)-positive individuals. METHODS An IRB-approved prospective study was conducted. The rapid screening pancreatic MR protocol was designed to be less than 10 min to be performed after a standard breast MRI protocol. Protocol consisted of coronal NT T2 SSFSE, axial NT T2 SSFSE and axial NT rFOV FOCUS DWI, and axial T1. Images were acquired with the patient in the same prone position of breast MRI using the built-in body coil. Image quality was qualitatively assessed by two radiologists with 12 and 13 years of MRI experience, respectively. The imaging protocol was modified until an endpoint of five consecutive patients with high-quality diagnostic images were achieved. Signal-to-noise ratio and contrast-to-noise ratio were assessed. RESULTS The rapid pancreas MR protocol was successfully completed in all patients. Diagnostic image quality was achieved for all patients. Excellent image quality was achieved for low b values; however, image quality at higher b values was more variable. In one patient, a pancreatic neuroendocrine tumor was found and the patient was treated surgically. In four patients, small pancreatic cystic lesions were detected. In one subject, a hepatic mass was identified and confirmed as adenoma by liver MRI. CONCLUSION Rapid MR protocol for pancreatic cancer screening is feasible and has the potential to play a role in screening BRCA patients undergoing breast MRI. KEY POINT • Develop and optimize a rapid magnetic resonance imaging (MRI) screening protocol for pancreatic cancer to be performed in conjunction with breast MRI screening in BRCA mutation positive individuals.
Collapse
Affiliation(s)
- Giuseppe Corrias
- Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA
- Department of Radiology, University of Cagliari, Cagliari, Italy
| | - Mitchell C Raeside
- Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA
| | - Andrea Agostini
- Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA
- Department of Radiology, Università Politecnica delle Marche, Ancona, Italy
| | | | - David Aramburu-Nunez
- Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Ramesh Paudyal
- Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Amita Shukla-Dave
- Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA
- Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Olga Smelianskaia
- Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA
| | - Marinela Capanu
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Junting Zheng
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Maggie Fung
- GE Healthcare, Global MR Applications and Workflow, New York, NY, USA
| | - David P Kelsen
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Debra A Mangino
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Mark E Robson
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Deborah J Goldfrank
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Jean Carter
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Peter J Allen
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Bettina Conti
- Policlinico Umberto I, Department of Radiology, Sapienza University of Rome, Rome, Italy
| | | | - Richard K G Do
- Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA
| | - Lorenzo Mannelli
- Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA.
| |
Collapse
|
|
48
|
de Mestier L, Muller M, Cros J, Vullierme MP, Vernerey D, Maire F, Dokmak S, Rebours V, Sauvanet A, Lévy P, Hammel P. Appropriateness of pancreatic resection in high-risk individuals for familial pancreatic ductal adenocarcinoma: a patient-level meta-analysis and proposition of the Beaujon score. United European Gastroenterol J 2019; 7:358-368. [PMID: 31019704 DOI: 10.1177/2050640618824910] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2018] [Accepted: 12/19/2018] [Indexed: 02/06/2023] Open
Abstract
Background About 5% of pancreatic ductal adenocarcinomas are inherited due to a deleterious germline mutation detected in 20% or fewer families. Pancreatic screening in high-risk individuals is proposed to allow early surgical treatment of (pre)malignant lesions. The outcomes of pancreatic surgery in high-risk individuals have never been correctly explored. Objectives To evaluate surgical appropriateness and search for associated factors in high-risk individuals. Methods A patient-level meta-analysis was performed including studies published since 1999. Individual classification distinguished the highest risk imaging abnormality into low-risk or high-risk abnormality, and the highest pathological degree of malignancy of lesions into no/low malignant potential or potentially/frankly malignant. Surgical appropriateness was considered when potentially/frankly malignant lesions were resected. Results Thirteen out of 24 studies were selected, which reported 90 high-risk individuals operated on. Low-risk/high-risk abnormalities were preoperatively detected in 46.7%/53.3% of operated high-risk individuals, respectively. Surgical appropriateness was consistent in 38 (42.2%) high-risk individuals, including 20 pancreatic ductal adenocarcinomas (22.2%). Identification of high-risk abnormalities was strongly associated with surgical appropriateness at multivariate analysis (P = 0.001). We proposed a score and nomogram predictive of surgical appropriateness, including high-risk abnormalities, age and existence of deleterious germline mutation. Conclusion Overall, 42.2% of high-risk individuals underwent appropriate surgery. The proposed score might help selecting the best candidates among high-risk individuals for pancreatic resection.
Collapse
Affiliation(s)
- Louis de Mestier
- Department of Gastroenterology and Pancreatology, Beaujon Hospital (AP-HP) and University Paris Diderot, Clichy, France
| | - Marie Muller
- Department of Digestive Oncology and Genetic Counselling, Beaujon Hospital (AP-HP) and University Paris Diderot, Clichy, France
| | - Jérôme Cros
- Department of Pathology, Beaujon Hospital (AP-HP) and University Paris Diderot, Clichy, France
| | - Marie-Pierre Vullierme
- Department of Radiology, Beaujon Hospital (AP-HP) and University Paris Diderot, Clichy, France
| | - Dewi Vernerey
- Department of Methodology and Quality of Life in Oncology Unit, EA 3181, Minjoz University Hospital, Besançon, France
| | - Frédérique Maire
- Department of Gastroenterology and Pancreatology, Beaujon Hospital (AP-HP) and University Paris Diderot, Clichy, France
| | - Safi Dokmak
- Department of Hepatobiliary and Pancreatic Surgery, Beaujon Hospital (AP-HP) and University Paris Diderot, Clichy, France
| | - Vinciane Rebours
- Department of Gastroenterology and Pancreatology, Beaujon Hospital (AP-HP) and University Paris Diderot, Clichy, France
| | - Alain Sauvanet
- Department of Hepatobiliary and Pancreatic Surgery, Beaujon Hospital (AP-HP) and University Paris Diderot, Clichy, France
| | - Philippe Lévy
- Department of Gastroenterology and Pancreatology, Beaujon Hospital (AP-HP) and University Paris Diderot, Clichy, France
| | - Pascal Hammel
- Department of Digestive Oncology and Genetic Counselling, Beaujon Hospital (AP-HP) and University Paris Diderot, Clichy, France
| |
Collapse
|
|
49
|
Abstract
Selective screening for pancreatic cancer (PC) has been proposed. We describe the establishment of a comprehensive multidisciplinary screening program using 3.0 T MRI. Criteria for screening included the presence of PC in: ≥ 2 first degree relatives (FDR), 1 FDR and 1 s degree relative (SDR), ≥ 3 any degree relatives (ADR), or any known hereditary cancer syndrome with increased PC risk. Imaging with 3.0 T MRI was performed routinely and endoscopic ultrasound was used selectively. Screening was completed in 75 patients (pts). Hereditary cancer syndromes were present in 42 (56%) of the 75 pts: BRCA2 (18), ATM (8), BRCA1 (6), CDKN2A (4), PALB2 (3), Lynch (2), and Peutz-Jeghers (1). A family history of PC was present in ≥ 2 FDR in 12 (16%) pts, 1 FDR and 1 SDR in 5 (7) pts, and ≥ 3 ADR in 16 (21%) pts. Of the 65 pts who received screening MRI, 28 (43%) pts had pancreatic cystic lesions identified, including 1 (1%) patient in whom a cholangiocarcinoma was diagnosed as well. No patient underwent surgical resection. Using a 3.0 T MRI to screen patients at high risk for developing PC identified radiographic abnormalities in 43% of patients, which were stable on subsequent surveillance. Specific guidelines for the frequency of surveillance and indications for surgery remain areas of active investigation as the global experience with high risk screening continues to mature.
Collapse
|
|
50
|
Cazacu IM, Luzuriaga Chavez AA, Saftoiu A, Bhutani MS. Psychological impact of pancreatic cancer screening by EUS or magnetic resonance imaging in high-risk individuals: A systematic review. Endosc Ultrasound 2019; 8:17-24. [PMID: 30246710 PMCID: PMC6400091 DOI: 10.4103/eus.eus_25_18] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Background and Objectives: There is an increasing global interest in screening programs aiming to detect pancreatic cancer (PC) in an early and potentially curable stage. Concerns still remain as to whether screening would confer any survival benefit. Another approach to evaluate the benefits of the pancreatic screening programs would be to consider its impact on the quality of life of the individuals who at risk of developing cancer. The aim of this systematic review was to investigate the current knowledge regarding the psychological impact of participation in routine screening for PC. Methods: A systematic literature search was carried out in January 2018 in three major databases which are as follows: PubMed, Scopus, and Web of Science. Cross-sectional and prospective studies evaluating the psychological aspects of screening in high-risk individuals were included in the study. For each study, the following data were recorded: name of first author, year of publication, study design, study population, aims, screening protocol, outcomes and instruments, main results, and summary of findings. Results: Six cohort studies and one cross-sectional study that addressed the psychological aspects of PC screening were included in the analysis. Overall, studies have shown that high-risk individuals have positive psychological outcomes from participating in PC screening programs. Conclusions: Although screening might not always be reassuring, it may improve individuals’ quality of life, and this should be an important aspect when considering PC screening.
Collapse
Affiliation(s)
- Irina Mihaela Cazacu
- Department of Gastroenterology, Hepatology and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA; Department of Gastroenterology, Research Center of Gastroenterology and Hepatology, University of Medicine and Pharmacy Craiova, Craiova, Romania
| | | | - Adrian Saftoiu
- Department of Gastroenterology, Research Center of Gastroenterology and Hepatology, University of Medicine and Pharmacy Craiova, Craiova, Romania
| | - Manoop S Bhutani
- Department of Gastroenterology, Hepatology and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| |
Collapse
|