Familial pancreatic carcinoma (FPC) is a rare hereditary tumor syndrome with a heterogeneous clinical phenotype. The study of FPC also contributes to a better understanding of the more common sporadic pancreatic ductal adenocarcinoma (PDAC). We report on the past 20 years' experience of the German National Case Collection for Familial Pancreatic Carcinoma (FaPaCa) of the German Cancer Aid (Deutsche Krebshilfe). From 1999 onward, families in which at least two first-degree relatives had PDAC, and which did not meet the criteria for any other tumor syndrome, have been entered into the FaPaCa registry and analyzed both clinically and with molecular genetic techniques. Persons at risk are offered the opportunity to participate in an early detection program. From June 1999 to June 2019, 227 families (a total of 2579 persons) met the criteria for entry into the FaPaCa registry. PDAC was the sole tumor entity present in 37% of the families (95% confidence interval [31.1; 44.1]); in the remaining 63% [55.9; 68.9], other tumor types were present as well, particularly breast cancer (70 families, 31% [24.9; 37.3]), colon carcinoma (25 families, 11% [7.3; 15.8]) , and melanoma (22 families, 9.7% [6.2; 14.3]). The mode of inheritance of PDAC was autosomal dominant in 72% [65.5; 77.6] of the families. Predisposing germ-line mutations were found in 25 of the 150 (16.7%) families studied, in the following genes: BRCA2 (9 families), CDKN2A (5 families), PALB2 (4 families), BRCA1 (3 families), ATM (2 families), and CHEK2 (2 families). The early detection program revealed high-grade cancer precursor lesions or a PDAC in 5 of the participating 110 persons at risk (4.5%, [1.5; 10.3] during a period of observation of at least five years. The care of families with FPC is complex and should be provided in centers with the necessary expertise. Prospective, controlled longitudinal studies are needed to determine whether the screening of persons at risk for PDAC truly lessens mortality and is cost-effective.

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. 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. 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. 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.

Pancreatic cancer is associated with poor survival and quality of life. In Romania the prognostic influence of known risk factors for pancreatic adenocarcinoma, such as age, smoking, chronic pancreatitis, diabetes mellitus, and obesity is little known. Their importance in developing cancer in families with a history of adenocarcinoma is less studied. This study aims to assess the risk factors in pancreatic ductal adenocarcinoma, in familial pancreatic adenocarcinoma, in neuroendocrine tumors and to evaluate their predictive role on survival. We performed a prospective bicentric study of patients with pancreatic tumors detected in transabdominal imaging; we assessed the risk factors and their possible association with survival. 312 pancreatic cancer patients (279 with pancreatic ductal adenocarcinoma and 24 patients with neuroendocrine tumors, and nine patients with other malignant types) and 312 controls were included. The median body mass index was significantly higher in patients with neuroendocrine tumors. Positive family history for pancreatic cancer was found in 4% of patients with pancreatic cancer. The risk for familial pancreatic carcinoma was associated with the presence of new-onset diabetes (OR: 4.64, p=0.018). The multivariate logistic analysis suggested that advanced age (OR: 1.67), smoking (OR: 1.67), low body mass index (OR: 12.07), and diabetes (OR: 3.91) were risk factors for pancreatic cancer. The overall survival analysis after adjustment for age and tumor stage showed only advanced tumoral stage (HR=1.6, p=0.003) and metastasis as independent predicting factors (HR=1.67, p<0.001). Our study suggests that diabetes, smoking, underweight, and age over 60 years are risk factors for pancreatic cancer. Patients with a family history of pancreatic cancer, especially those with new-onset diabetes, should be followed carefully and considered for screening. Only an advanced tumor stage was associated with poor overall survival for patients with pancreatic ductal adenocarcinoma.

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. To evaluate surgical appropriateness and search for associated factors in high-risk individuals. 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. 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. 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.