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

Benchmarks in Liver Resection for Intrahepatic Cholangiocarcinoma

Introduction: Benchmarking in surgery has been proposed as a means to compare results across institutions to establish best practices. We sought to define benchmark values for hepatectomy for intrahepatic cholangiocarcinoma (ICC) across an international population. Methods: Patients who underwent liver resection for ICC between 1990 and 2020 were identified from an international database, including 14 Eastern and Western institutions. Patients operated on at high-volume centers who had no preoperative jaundice, ASA class &lt;3, body mass index &lt;35 km/m2, without need for bile duct or vascular resection were chosen as the benchmark group. Results: Among 1193 patients who underwent curative-intent hepatectomy for ICC, 600 (50.3%) were included in the benchmark group. Among benchmark patients, median age was 58.0 years (interquartile range [IQR] 49.0–67.0), only 28 (4.7%) patients received neoadjuvant therapy, and most patients had a minor resection (n = 499, 83.2%). Benchmark values included ≥3 lymph nodes retrieved when lymphadenectomy was performed, blood loss ≤600 mL, perioperative blood transfusion rate ≤42.9%, and operative time ≤339 min. The postoperative benchmark values included TOO achievement ≥59.3%, positive resection margin ≤27.5%, 30-day readmission ≤3.6%, Clavien-Dindo III or more complications ≤14.3%, and 90-day mortality ≤4.8%, as well as hospital stay ≤14 days. Conclusions: Benchmark cutoffs targeting short-term perioperative outcomes can help to facilitate comparisons across hospitals performing liver resection for ICC, assess inter-institutional variation, and identify the highest-performing centers to improve surgical and oncologic outcomes.</p

Benchmarks in Liver Resection for Intrahepatic Cholangiocarcinoma

Introduction: Benchmarking in surgery has been proposed as a means to compare results across institutions to establish best practices. We sought to define benchmark values for hepatectomy for intrahepatic cholangiocarcinoma (ICC) across an international population. Methods: Patients who underwent liver resection for ICC between 1990 and 2020 were identified from an international database, including 14 Eastern and Western institutions. Patients operated on at high-volume centers who had no preoperative jaundice, ASA class &lt;3, body mass index &lt;35 km/m2, without need for bile duct or vascular resection were chosen as the benchmark group. Results: Among 1193 patients who underwent curative-intent hepatectomy for ICC, 600 (50.3%) were included in the benchmark group. Among benchmark patients, median age was 58.0 years (interquartile range [IQR] 49.0–67.0), only 28 (4.7%) patients received neoadjuvant therapy, and most patients had a minor resection (n = 499, 83.2%). Benchmark values included ≥3 lymph nodes retrieved when lymphadenectomy was performed, blood loss ≤600 mL, perioperative blood transfusion rate ≤42.9%, and operative time ≤339 min. The postoperative benchmark values included TOO achievement ≥59.3%, positive resection margin ≤27.5%, 30-day readmission ≤3.6%, Clavien-Dindo III or more complications ≤14.3%, and 90-day mortality ≤4.8%, as well as hospital stay ≤14 days. Conclusions: Benchmark cutoffs targeting short-term perioperative outcomes can help to facilitate comparisons across hospitals performing liver resection for ICC, assess inter-institutional variation, and identify the highest-performing centers to improve surgical and oncologic outcomes.</p

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