Hereditary pancreatic cancer

Pancreatic cancer is associated with both family and hereditary cancer syndromes. Multigene panel testing for pancreatic cancer detected the germline variants BRCA1/2, PALB2, ATM, TP53, MLH1, STK11/LKB1, APC, CDKN2A, and SPINK1/ PRSS1 as high-risk genes. A latest genome-wide association study revealed the common, but low-risk germline variants in pancreatic cancer patients. Active pancreatic surveillance using magnetic resonance imaging and endoscopic ultrasound is recommended for high-risk individuals who have a family history of pancreatic cancer or harbor these germline pathogenic variants to improve the detection rate and prognosis of pancreatic cancer. Since poly-ADP-ribose polymerase (PARP) inhibitor has been shown to be effective in improving the prognosis of BRCA -positive pancreatic cancer as well as hereditary breast and ovarian cancer syndrome, PARP inhibitor therapy is currently being applied as precision medicine to pancreatic cancer patients harboring the BRCA1/2 germline variant. This review highlights the importance of surveillance for germline pathogenic variants in pancreatic cancer and is expected to lead to improvements in the diagnosis and prevention of pancreatic cancer as well as facilitate the development of effective therapeutic strategies and precision medicine

Familial pancreatic cancer with PALB2 and NBN pathogenic variants: a case report

Background Family history is one of the risk factors for pancreatic cancer. It is suggested that patients with pancreatic cancer who have a familial history harbor germline pathogenic variants of BRCA1 and/or BRCA2 (BRCA1/2), PALB2, or ATM. Recently, some germline variants of familial pancreatic cancers (FPCs), including PALB2, have been detected. Several countries, including Japan, perform screening workups and genetic analysis for pancreatic cancers. We have been carrying out active surveillance for FPC through epidemiological surveys, imaging analyses, and genetic analysis. Case presentation Here, we present the case of a female patient harboring pathogenic variants of PALB2 and NBN, with a family history of multiple pancreatic cancer in her younger brother, her aunt, and her father. Moreover, her father harbored a PALB2 pathogenic variant and her daughter harbored the same NBN pathogenic variant. Given the PALB2 and NBN variants, we designed surveillance strategies for the pancreas, breast, and ovary. Conclusions Further studies are required to develop strategies for managing FPCs to facilitate prompt diagnosis before their progression

Predictive factors of late cholangitis in patients undergoing pancreaticoduodenectomy

Abstract Background Because the survival rate for patients experiencing late complications after pancreaticoduodenectomy (PD) is increasing, late complications should receive as much attention as early complications do. Methods Between April 2007 and August 2016, 133 patients underwent PD at our institution. We analyzed their cases to determine the predictors of late cholangitis after PD. Results Of the 133 patients, 28 (21.1%) were diagnosed with postoperative cholangitis. A multivariate analysis showed that abnormal postoperative values of alkaline phosphatase were independently associated with postoperative cholangitis (odds ratio, 3.81; 95% confidence interval, 1.519–9.553; P = 0.004). The optimal cut-off value for postoperative alkaline phosphatase calculated from the receiver operating characteristic curve was 410 IU/L (sensitivity, 76.2%; specificity, 67.9%; area under the curve, 0.73). A univariate analysis to identify risk factors showed that pneumobilia was significantly related to a postoperative alkaline phosphatase value ≥ 410 IU/L (P = 0.041). Conclusion This study suggests that an alkaline phosphatase level ≥ 410 IU/L is a predictor of late postoperative cholangitis. In addition, pneumobilia is also related to the postoperative alkaline phosphatase level. Therefore, alkaline phosphatase levels should be carefully monitored in patients with postoperative pneumobilia in the late postoperative course

Predictive Factors of Early Recurrence in Patients with Distal Cholangiocarcinoma after Pancreaticoduodenectomy

Aim. To determine the factors associated with early recurrence in patients with distal cholangiocarcinoma after pancreaticoduodenectomy (PD). Patients and Methods. Sixty-one patients with distal cholangiocarcinoma were enrolled. The clinical data and histopathological findings were collected retrospectively. Results. Patients were divided into two groups as follows: 16 patients (26%) with early recurrence and 45 patients (74%) with late recurrence or no recurrence. In a univariate analysis, lymph node metastases (P=0.0016), lymphatic invasion (P<0.0001), pancreatic invasion (P=0.0006), and perineural invasion (P=0.0004) were significantly different between the two groups. In a multivariate analysis, a higher incidence of lymphatic invasion was the only independent risk factor for early recurrence (odds ratio: 5.772, 95% confidence interval: 1.123–29.682, P=0.036). Moreover, the disease-free survival and overall survival of patients with a higher incidence of lymphatic invasion were significantly worse compared with those of patients with a lower incidence of lymphatic invasion (P<0.001). Conclusions. Our study showed that a higher incidence of lymphatic invasion was a significant predictor of early recurrence in patients with distal cholangiocarcinoma. Therefore, lymphatic invasion might be useful in determining the optimal adjuvant therapy in the early postoperative stage for distal cholangiocarcinoma