Surveillance in patients with chronic pancreatitis or hereditary risks
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1 European Digestive Cancer Days th September Prague Surveillance in patients with chronic pancreatitis or hereditary risks J. Rosendahl Universitätsklinik für Innere Medizin I Universitätsklinikum Halle (Saale)
2 Surveillance in patients Pankreaskarzinom with chronic pancreatitis - CP or hereditary risks - Cancer risk in Chronic Pancreatitis patients - Is Pancreatic Cancer a real burden - Influence of Aetiology - Lag between Chronic Pancreatitis and Cancer development - Hereditary Chronic Pancreatitis - Precursor lesions Early detectable? - Mutations and Pancreatic Cancer development - Surveillance strategies - Lessons from familial Pancreatic Cancer
3 Cancer types Tod, in Malignome Chronic Pancreatitis und Komorbiditäten (CP) patients? bei CP - Retrospective cohort study ( ) CP patients ( person years), controls ( person years) - 46% patients died vs. 13% controls (HR 5.0, 95% CI ) - Cancer deaths: 10.2% pat. vs. 3.3% controls (HR 6.9, 95% CI ) Bang et al., Gastroenterology 2014
4 Risk of death in CP Risiko patients zu sterben - Todesrate Bang et al., Gastroenterology 2014
5 Are other cancer types even Malignome more important? bei CP Bang et al., Gastroenterology 2014
6 Kumulative Inzidenz (%) Pancreatic cancer risk CP RR 13.3 ( ) RR 69.0 ( ) Relative risk (95% CI) Raimondi et al., Best Pract Res Clin Gastroenterol 2010
7 Pancreatic cancer risk CP (lag period?) Kirkekârd et al., Am J Gastroenterol 2017
8 Surveillance in patients Pankreaskarzinom with chronic pancreatitis - CP or hereditary risks - Cancer risk in Chronic Pancreatitis patients - Is Pancreatic Cancer a real burden - Influence of Aetiology - Lag between Chronic Pancreatitis and Cancer development - Hereditary Chronic Pancreatitis - Precursor lesions Early detectable? - Mutations and Pancreatic Cancer development - Surveillance strategies - Lessons from familial Pancreatic Cancer
9 Histological results of operated patients with inherited CP Median 24 years Rebours et al., Clin Gastroenterol Hepatol 2010
10 Diagnosed (%) EUROPAC Risk to develop Pancreatic Carcinoma n=418 59% 22% 19% Age (years) Howes et al., Clin Gastroenterol Hepatol 2004
11 Age at diagnosis (years) Pancreatic cancer CP and Smoking Onset of the disease 20 years earlier Ever smoker Never smoker Lowenfels et al., JAMA 2001
12 Surveillance in patients Pankreaskarzinom with chronic pancreatitis - CP or hereditary risks - Cancer risk in Chronic Pancreatitis patients - Is Pancreatic Cancer a real burden - Influence of Aetiology - Lag between Chronic Pancreatitis and Cancer development - Hereditary Chronic Pancreatitis - Precursor lesions Early detectable? - Mutations and Pancreatic Cancer development - Surveillance strategies - Lessons from familial Pancreatic Cancer
13 Screening seems feasible?
14 Endoscopic ultrasound in CP
15 Screening? Comparison with familial Pancreatic cancer Bartsch et al., Fam Cancer 2013
16 Surveillance Who should be screened? Vasen et al., J Clin Oncol 2016
17 Pancreatic Cancer in CDKN2A/p16 mutation carriers 13/178 (7.3%) Average follow-up 4.4 month Vasen et al., J Clin Oncol 2016
18 Overall survival in CDKN2A/p16 mutation carriers 5-year survival rate 24% (Sporadic Pancreatic Cancer approx. 4-7%) Vasen et al., J Clin Oncol 2016
19 Overall survival in CDKN2A/p16 mutation carriers 5-year survival rate 24% Familial Pancreatic Cancer group: 2/214 (0.9%) Pancreatic Tumor (one Pancreatic Cancer) 13/214 (6.1%) underwent resection 4 had High grade lesions Vasen et al., J Clin Oncol 2016
20 Signature of metabolites A promising approach... Mayerle et al., GUT 2017
21 Signature of metabolites A promising approach... Mayerle et al., GUT 2017
22 Signature of metabolites A promising approach... Mayerle et al., GUT 2017
23 Signature of metabolites A promising approach... Mayerle et al., GUT 2017
24 Thrombospondin-2 and CA19-9 A promising approach... Combining CA19-9 and THBS2 Sensitivity 87% Specificity 98% Kim et al., Sci Transl Med 2017
25 Urine peptide panel A promising approach... >37 U/mL Schönemeier et al., Pancreas 2016
26 Surveillance in patients Pankreaskarzinom with chronic pancreatitis - CP or hereditary risks Conclusion: - Pancreatic Cancer is a real burden for Chronic Pancreatitis patients - Early onset of Chronic Pancreatitis increases risk to develop Pancreatic Cancer - Surveillance strategies need improvement as demonstrated in familial Pancreatic Cancer - Are new Biomarkers the solution? - Relatives Risiko 5,7 (95% CI
27 Thank you!
28 Signature of metabolites A promising approach... Mayerle et al., GUT 2017
29 Familiäres Pankreaskarzinom - Screening Habbe et al., Chirurg 2008
30 Gut Aug;65(8): doi: /gutjnl Epub 2016 May 24. Refinement of screening for familial pancreatic cancer. Bartsch DK 1, Slater EP 1, Carrato A 2, Ibrahim IS 3, Guillen-Ponce C 2, Vasen HF 3, Matthäi E 1, Earl J 2, Jendryschek FS 1, Figiel J 4, Steinkamp M 5, Ramaswamy A 6, Vázquez-Sequeiros E 7, Muñoz-Beltran M 8, Montans J 9, Mocci E 2, Bonsing BA 10, Wasser M 11, Klöppel G 12, Langer P 13, Fendrich V 1, Gress TM 5. Author information Abstract OBJECTIVE: Surveillance programmes are recommended for individuals at risk (IAR) of familial pancreatic cancer (FPC) to detect early pancreatic cancer (pancreatic ductal adenocarcinoma, PDAC). However, the age to begin screening and the optimal screening protocol remain to be determined. METHODS: IAR from non-cdkn2a FPC families underwent annual screening by MRI with endoscopic ultrasonography (EUS) in board-approved prospective screening programmes at three tertiary referral centres. The diagnostic yield according to age and different screening protocols was analysed. RESULTS: 253 IAR with a median age of 48 (25-81) years underwent screening with a median of 3 (1-11) screening visits during a median follow-up of 28 (1-152) months. 134 (53%) IAR revealed pancreatic lesions on imaging, mostly cystic (94%), on baseline or follow-up screening. Lesions were significantly more often identified in IAR above the age of 45 years (p<0.0001). In 21 IAR who underwent surgery, no significant lesions (PDAC, pancreatic intraepithelial neoplasia (PanIN) 3 lesions, high-grade intraductal papillary mucinous neoplasia (IPMN)) were detected before the age of 50 years. Potentially relevant lesions (multifocal PanIN2 lesions, low/moderate-grade branch-duct IPMNs) occurred also significantly more often after the age of 0 years (13 vs 2, p<0.0004). The diagnostic yield of potentially relevant lesions was not different between screening protocols using annual MRI with EUS n=98) or annual MRI with EUS every 3rd year (n=198) and between IAR screened at intervals of 12 months (n=180) or IAR that decided to be screened a 24 months intervals (n=30). CONCLUSIONS: It appears safe to start screening for PDAC in IAR of non-cdkn2a FPC families at the age of 50 years. MRI-based screening supplemented by EUS at baseline and every 3rd year or when changes in MRI occur appears to be efficient.
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