Early detection and prevention of pancreatic cancer: Is it really possible today?

Table 1 Non-genetic factors associated with an increased risk to develop pancreatic cancer

Risk factors	Estimated overall risk	Ref.
Smoking	1.75	[37,38]
Overweight	1.12 per increased 5 kg/m2	[39-41]
Alchohol abuse	1.2	[42,43]
Type 1 diabetes	2.0	[44]
New onset type 2 diabetes	2.0	[45]
Chronic pancreatitis	14.0	[46]
Exposure to nickel	1.9	[47]
Previous gastric ulcer	1.8	[48]

Table 2 Most important genetic syndromes associated with an increased risk of pancreatic cancer

Syndrome	Gene	Relative risk	Risk at age of 70
Familial pancreatic cancer	Unknown
1 or more first degree relative(s)		9	4%
1 first degree relative		4.5	2%
2 first degree relatives		6.4	3%
3 or more first degree relatives		32	16%
Peutz Jeghers syndrome	LKB1/STK11	132	30%-60%
Hereditary pancreatitis	PRSS1	50-70	40%
Familial atypical multiple mole melanoma	CDKN2A/p16	34-39	17%
Breast and ovarian cancer syndrome	BRCA1/BRCA2	2.3-10	1%-5%
Cystic fibrosis	CFTR	5.3	< 5%
Hereditary non-polyposis colon cancer	MSH2, MLH1, MSH6, PMS, PMS2	4.7	< 5%
Familial adenomatous polyposis	APC	4.5	2%

LKB1/STK1: Liver kinase B1/serine-threonine kinase 11; PRSS1: Protease serine 1; CDKN2A/p16: Cyclin-dependent kinase Inhibitor 2A; BRCA1/BRCA2: Breast cancer type 1 and 2 proteins; CFTR: Cystic fibrosis transmembrane conductance regulator; MSH2: DNA mismatch repair protein Msh2; MLH1: MutL homolog 1, colon cancer, nonpolyposis type 2; MSH6: MutS homolog 6; PMS, PMS2: Mismatch repair endonuclease.

Table 3 Characteristics related to epithelial subtype in intraductal papillary mucinous neoplasia

	Epithelial subtype
	Gastric	Intestinal	Pancreatobiliary	Oncocytic
Location	Branch duct > main duct	Main duct > branch duct	Branch duct > main duct	Branch duct > main duct
Dysplasia	LGD/IGD	IGD/HGD	HGD	HGD
Present with invasive carcinoma	15%	30%-60%	60%-75%	25%
Type of invasive carcinoma	Conventional (tubular)	Colloid or conventional (tubular)	Conventional (tubular)	Oncocytic or conventional (tubular)

LGD: Low-grade dysplasia; IGD: Intermediate-grade dysplasia; HGD: High-grade dysplasia.

Table 4 Incidence of cancer during follow-up of branch-duct intraductal papillary mucinous neoplasms of the pancreas

Ref.	Year	Patients (n)	Incidence of cancer on IPMN
Lafemina et al[97]	2013	170	11.0%
Sahora et al[98]	2013	240	4.0%1
Khannoussi et al[99]	2012	53	3.7%
Arlix et al[100]	2012	49	0
Maguchi et al[101]	2011	349	2.6%2
Salvia et al[102]	2009	121	0
Tanno et al[103]	2008	82	1.2%

¹Other 3.7% of patients developed a concurrent pancreatic cancer (PC);

²Other 0.8% of patients developed a concurrent PC. IPMN: Intraductal papillary mucinous neoplasms.

Table 5 Summary of diagnostic yield of familial pancreatic cancer screening

Ref.	Year	Syndrome(s)	Patients (n)	Yield
Brentnall et al[106]	1999	FPC	14	50%
Kimmey et al[107]	2002	FPC	46	26%
Poley et al[108]	2009	FPC, PJS, BRCA, p16, p53, HP	44	23%
Langer et al[109]	2009	FPC, BRCA	76	1.3%
Verna et al[110]	2010	FPC, BRCA, p16	51	12%
Ludwig et al[111]	2011	FPC, BRCA	109	8.3%
Vasen et al[112]	2011	P16	79	18%
Al-Sukhni et al[113]	2011	FPC, BRCA, PJS, p16, HP	262	7.3%
Schneider et al[114]	2011	FPC, BRCA, PALB2	72	15%
Canto et al[115]	2012	FPC, BRCA, PJS	216	43%

HP: Hereditary pancreatitis; FPC: Familial pancreatic cancer; PJS: Peutz-Jeghers syndrome; BRCA: Breast cancer.

Table 6 Surgical procedure performed in patients at ”hereditary risk” for pancreatic cancer (n)

Ref.	Year	Resected	PanIN1	PanIN2	PanIN3	Pancreas cancer	Other bening lesions	Other malignant lesions	Benign IPMN	Malignant or high-grade displasia IPMN	Malignant lesions or high-grade dysplasia1
Brentnall et al[106]	2006	7	-	2	2	-		-	2	1	42.8%
Poley et al[108]	2009	3	-	-	-	3		-	-	-	100%
Verna et al[110]	2010	5	-	-	-	1	-	-	4	-	20%
Ludwig et al[111]	2011	6	1	1	1	1	-	-	2	-	16.7%
Vasen et al[112]	2011	7	-	-	-	7	-	-	-	-	100%
Al-Sukhni et al[113]	2011	4	-	-	-	1	-	1	2	-	50%
Schneider et al[114]	2011	9	1	1	1	1	3	-	2	-	22.2%
Canto et al[115]	2012	5	-	-	1	-	-	-	3	1	40%
Total		46	2	4	5	14	3	1	15	2	47.8%

¹The percentage refers to all resected patients, not to all patients included in the study. IPMN: Intraductal papillary mucinous neoplasm; PanIN: Pancreatic intraepithelial neoplasia.