Role of endoscopic ultrasound in the screening and follow-up of high-risk individuals for familial pancreatic cancer

Table 1 Risk of pancreatic cancer based on genetic mutations

Condition	Gene	Relative risk of PC compared to the general population	Risk of pancreatic cancer at 70 yr (%)	% Among inherited cancers
No family history		1	0.5-1	?
2 first degree relatives with PC	Unknown	5-7	5-12	80-85
3 first degree relatives with PC	Unknown	32	40
Hereditary breast ovarian cancer syndrome	BRCA1	2-4	3-4	1-5
	BRCA2	2-10	4-5	5-20
Genetic pancreatitis	PRSS1	50-80	40-55	1-4
FAMMM	CDKN2A	10-25	5-25	2-3
Peutz-Jeghers syndrome	STK11	100-130	30-40	1-3
Lynch syndrome	MLH1, MSH2, MSH6, PMS2	4-8	3-5	1-3

PC: pancreatic cancer; FAMMM: Familial atypical multiple mole melanoma.

Table 2 Main characteristics of high-risk individuals for pancreatic cancer in the different studies

First author/yr	Setting	High risk condition	Patients included	Modalities of screening	Imaging results	Patients operated on	Operated lesions seen only by the EUS	Histological features with cancer or HGD
Brentnall et al[37]	Prospective, monocentric	FPC	14	EUS	CPis: 10 (77%) Cystic lesio: ? Solid lesio: 6 (46%)	7	1NA	7 dysplasia
Rulyak et al[38]	Prospective, monocentric	FPC	35	EUS, ERCP	12 lesions	12	?	12 dysplasia
Kimmey et al[78]	Prospective, monocentric	FPC	46	EUS, ERCP	CPis: 24 (52%) Cystic lesion: ? Solid lesion: 12 (26%)	?	?	?
Canto et al[12]	Prospective, monocentric	FPC, PJS,	38	EUS first, +/- ERCP, CT, FNA	CPis: 17 (45%) Cystic lesion: ? Solid lesion: 12 (31%)	7	2/7 (1 PC, 1 PanIN3)	1 PC 1 PanIN3
Canto et al[23]	Prospective, monocentric	FPC, PJS,	78	EUS, CT +/- ERCP, FNA	CPis: 61 (78%) Cystic lesion: 9 (12%) Solid lesion: 8 (10%)	7	3/7 (1 PanIN 3, 2 PanIN1-2)	1 PC+IPMN 1 PanIN3 1PanIN3+IPMN
Poley et al[13]	Prospective, multicentric	FPC, PJS, FAMMM, FBOC, HP, LFS	44	EUS	CPis: 3 (7%) Cystic lesion: 7 (16%) Solid lesion: 3 (7%)	10	1NA	3 PC
Langer et al[15]	Prospective, multicentric	FPC, FAMMM	76	EUS + MRI	CPis: 17 (22%) Cystic lesion: 3 (4%) Solid lesion: 7 (9%)	7	5/7 (9/21 non operated lesions seen only in EUS)	0 PC or PanIN3 or IPMN with HGD
Verna et al[33]	Prospective, monocentric	FPC, FBOC	51	EUS n = 31 or MRI n = 33 +/- ERCP, FNA	CPis: 9 (29%) Cystic lesion: 12 (39%) Solid lesion: 2 (6%)	5	? (2 solid lesions in EUS and MRI)	1 PC 1 PanIN2
Ludwig et al[34]	Prospective, monocentric	FPC	109	MRCP or CT EUS, FNA	18 lesions	6	?	1 PC 2 MD IPMN 1 PanIN-3 1 PanIN-2
Schneider et al[40]	Prospective, monocentric	FPC, FAMMM	72	EUS, MRI	13 lesions	9	?	1 PC 1 PanIN-3
Zubarik et al[16]	Prospective, monocentric	FPC, PJS, BRCA2	27	CA19-9 +/- EUS (27/546)	5 lesions	5	1NA	1 PC
Canto et al[25]	Prospective, multicentric	FPC, FBOC, PJS	216	CT, EUS, MRI/MRCP	CPis: 54 (25%) Cystic lesion: 79 (36%) Solid lesion: 3 (1.4%)	5	? (20/216 non operated lesions seen only in EUS including 3 solid lesion)	2 MD-IPMN 1 IPMN+PanIN3
Al-Sukhni et al[32]	Prospective, monocentric	FPC, BRCA1/2, FAMMM, LKB1	252	MRI, +/- CT, EUS, ERCP	CPis: ? Cystic lesion: 80 (32%) Solid lesion: 3 (1.2%)	4		3 PC
Sud et al[14]	Prospective, monocentric	FPC, BRCA1/2, MMR, CDKN2A, LKB1, PRSS1	30	EUS +/- FNA	3 lesions	3	1NA	2 PC
Mocci et al[10]	Prospective, multicentric	FPC, CDKN2A, MMR, PRSS1	41	EUS, CT +/- MRI, FNA	CPis: 15 (37%) Cystic lesion:4 (10%) Solid lesion: 2 (5%)	1	2NA	1 NET 1 PanIN3
Vasen et al[31]	Prospective, multicentric	FPC, CDKN2A, BRCA 1/2	411	MRI, EUS, CT, FNA	CPis: ? Cystic lesion: 138 (34%) Solid lesion: 16 (4%)	30	2/30 (866 MRIs and 106 EUS performed)	16 PC 3 PanIN3 1 IPMN with high grade
Bartsch et al[4]	Prospective, multicentric	FPC, BRCA1/2, PALB2	234	MRI, EUS, CT, FNA	CPis: ? Cystic lesion: 125 (49%) Solid lesion: 9 (4%)	21 6/253 (2%) lesions (2 malignant and HGD)	?	2 PC 3 PanIN3 1 IPMN with HGD; multifocal PanIN2±BD-IPMN±AFL 1 NET 8 PanIN-2
Harinck et al[27]	Prospective, multicentric	FPC, BRCA1/2, CDKN2A, LKB1, TP53, MMR	139	MRI +/- EUS	CPis: 41 (30%) Cystic lesion: 67 (48%) Solid lesion: 2 (1.4%)	2	2/2 (1 PC, 1 PanIN-2)	1 PC 1 PanIN-2

¹NA: Not applicable, because patients had only endoscopic ultrasound (EUS);

²NA: Not applicable, because patients had an EUS only if magnetic resonance imaging was abnormal. Three patients developed pancreatic cancer during the screening. CPis: Chronic-pancreatitis-like parenchymal changes; CT: Computed tomography; EUS: Endoscopic ultrasound; FNA: Fine needle aspiration; FPC: Familial pancreatic cancer; IPMN: Intraductal papillary mucinous neoplasm; MRI: Magnetic resonance imaging; PanIN: Pancreatic intraneoplasia; PC: Pancreatic cancer; ERCP: Endoscopic retrograde cholangiopancreaticography; HGD: High-grade dysplasia.