764 International Consensus Recommendations on the Management of Patients With Increased Risk for Familial Pancreatic Cancer: Cancer of the Pancreas Screening Consortium (CAPS) 2011 Summit

Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
Gut (Impact Factor: 14.66). 11/2012; 62(3). DOI: 10.1136/gutjnl-2012-303108
Source: PubMed


Background Screening individuals at increased risk for pancreatic cancer (PC) detects early, potentially curable, pancreatic neoplasia.
Objective To develop consortium statements on screening, surveillance and management of high-risk individuals with an inherited predisposition to PC.
Methods A 49-expert multidisciplinary international consortium met to discuss pancreatic screening and vote on statements. Consensus was considered reached if ≥75% agreed or disagreed.
Results There was excellent agreement that, to be successful, a screening programme should detect and treat T1N0M0 margin-negative PC and high-grade dysplastic precursor lesions (pancreatic intraepithelial neoplasia and intraductal papillary mucinous neoplasm). It was agreed that the following were candidates for screening: first-degree relatives (FDRs) of patients with PC from a familial PC kindred with at least two affected FDRs; patients with Peutz–Jeghers syndrome; and p16, BRCA2 and hereditary non-polyposis colorectal cancer (HNPCC) mutation carriers with ≥1 affected FDR. Consensus was not reached for the age to initiate screening or stop surveillance. It was agreed that initial screening should include endoscopic ultrasonography (EUS) and/or MRI/magnetic resonance cholangiopancreatography not CT or endoscopic retrograde cholangiopancreatography. There was no consensus on the need for EUS fine-needle aspiration to evaluate cysts. There was disagreement on optimal screening modalities and intervals for follow-up imaging. When surgery is recommended it should be performed at a high-volume centre. There was great disagreement as to which screening abnormalities were of sufficient concern to for surgery to be recommended.
Conclusions Screening is recommended for high-risk individuals, but more evidence is needed, particularly for how to manage patients with detected lesions. Screening and subsequent management should take place at high-volume centres with multidisciplinary teams, preferably within research protocols.

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Available from: George Johan A Offerhaus, Jan 24, 2014
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    • "Canto M.I. and associates investigated the occurrence of pancreatic cancer and connects it with the genetic mutations, as well as with age and is considered that family history has an impact on the development of pancreatic cancer. In his research he concluded that EUS and MRI are better in detecting small pancreatic tumors then CT and that EUS detected significantly fewer lesions than CT in 42.6% of cases as our study show because in the detection of the size and location of tumor lesions EUS was ahead of CT and CTA (9). "
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    ABSTRACT: The goal: The goal of this work was to give advantage to EUS as endoscopic method in diagnosis and following therapeutic treatment of pancreatic cancer in relation to radiological methods of CT and CTA. Material and Methods: The study included 49 patients, 20 women and 29 men hospitalized at the Clinic for gastroenterohepatology, due to suspicion on pancreatic cancer during observed 2 years period. All cancers were histologically and cytologically confirmed. The patients underwent ERCP as a mandatory part of staging and all patients underwent endoscopic ultrasound as well as CT or CT angiography. Results: Testing of differences was carried out using Fisher’s exact test in open-source software R. The following characteristics were tested: involvement of the blood vessels, lymph nodes, metastases, tumor size and duodenum infiltration. Results showed statistically significant difference at the 0.05 level for EUS, CT and CT angiography. Risk ratio showed that EUS is less effective in detecting infiltration of blood vessels within a malignant process then CTA where RR=0.52, CI 0.2–1.38, p-value=0.33. EUS and CTA are equal in the diagnosis of enlarged lymph nodes affected by malignancy where RR=1.3, CI 0.75–1.42, p-value=0.09. Comparison according to distant metastases showed that EUS is less effective compared to CT in approximately 30% of cases. In the diagnosis of duodenal infiltration EUS is in 5% of cases less accurate than the CT with the RR=0.95, CI 0.27–3.32, p-value=0.76, but the CTA method is more efficient because the comparison of EUS and CTA showed RR=12.52, CI 0.2–1.38, p-value=0.33. EUS as a diagnostic method is dominant in determining the size of malignant lesions located in the pancreas as compared to CT and CTA. Conclusion: EUS as endoscopic method compared to CT and CTA is one of the more invasive methods of examination but due to its ability to be performed immediately, to locate a changes smaller than 5 mm and the target biopsy option, to measure the change and that in many cases determine the relationship of malignant lesions with blood vessels, along with visualization of the surrounding lymph nodes and metastases in neighboring organs, we may give this method an advantage over other methods in the preoperative staging of patients with pancreatic cancer.
    Acta Informatica Medica 06/2014; 22(3):160-3. DOI:10.5455/aim.2014.22.160-163
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    • "These high-risk candidates for screening include first degree relatives of patients with PDAC from familial kindred with at least two affected first-degree relatives , patients with PJS, and carriers of p16, BRCA2, or HNPCC mutations with at least one affected first-degree relative. The CAPS Consortium was not able to reach a consensus on the age to initiate screening or stop surveillance, as well as screening intervals, although agreement was made that initial screening should include EUS and/or MRI/MRCP, and not CT or ERCP (Canto et al., 2013). At this time, based on the current knowledge of pancreatic susceptibility genes, affected patients of FPC families should consider being tested for the most frequently inherited genetic defects identified in FPC, BRCA2, PALB2, and ATM germline mutations. "
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    ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer deaths in both men and women in the United States, carrying a 5-year survival rate of approximately 5%, which is the poorest prognosis of any solid tumor type. Given the dismal prognosis associated with PDAC, a more thorough understanding of risk factors and genetic predisposition has important implications not only for cancer prevention, but also for screening techniques and the development of personalized therapies. While screening of the general population is not recommended or practicable with current diagnostic methods, studies are ongoing to evaluate its usefulness in people with at least 5- to 10-fold increased risk of PDAC. In order to help identify high-risk populations who would be most likely to benefit from early detection screening tests for pancreatic cancer, discovery of additional pancreatic cancer susceptibility genes is crucial. Thus, specific gene-based, gene-product, and marker-based testing for the early detection of pancreatic cancer are currently being developed, with the potential for these to be useful as potential therapeutic targets as well. The goal of this review is to provide an overview of the genetic basis for PDAC with a focus on germline and familial determinants. A discussion of potential therapeutic targets and future directions in screening and treatment is also provided.
    Frontiers in Physiology 03/2014; 5:87. DOI:10.3389/fphys.2014.00087 · 3.53 Impact Factor
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    ABSTRACT: Pancreatic cancer (PC) is one of the most challenging tumor entities worldwide, characterized as a highly aggressive disease with dismal overall prognosis and an incidence rate equalling mortality rate. Over the last decade, substantial progress has been made to define the morphological changes and key genetic events in pancreatic carcinogenesis. And yet, it is still unclear what factors trigger PC. Some risk factors appear to be associated with sex, age, race/ethnicity, or other rare genetic conditions. Additionally, modifying factors such as smoking, obesity, diabetes, occupational risk factors, etc., increase the potential for acquiring genetic mutations that may result in PC. Another hallmark of PC is its poor response to radio- and chemo-therapy. Current chemotherapeutic regimens could not provide substantial survival benefit with a clear increase in overall survival. Recently, several new approaches to significantly improve the clinical outcome of PC have been described involving downstream signaling cascades desmoplasia and stromal response as well as tumor microenvironment, immune response, vasculature, and angiogenesis. This review summarizes major risk factors for PC and tries to illuminate relevant targets considerable for new therapeutic approaches.
    Frontiers in Oncology 11/2013; 3:282. DOI:10.3389/fonc.2013.00282
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