The comprehensive genomic profiling (CGP) test using a multiplex gene panel has been reimbursed by the National Health Insurance System since June 2019. A liquid biopsy using blood specimens has been added as an option for CGP since August 2021. The results of CGP must be annotated by a molecular tumor board called an "expert panel", which includes multidisciplinary specialists. Currently, the indications for CGP are limited to patients with advanced solid tumors who have completed or are expected to complete standard treatment. Since it takes almost 6 to 8 weeks from the time of application for the CGP test until the results are returned to the patient, it is necessary to pay careful attention to this detail when applying for a CGP test for a patient with pancreatic cancer which often progresses in a short time and has a poor prognosis. Although the percentage of patients who receive treatment based on the results of CGP test is less than 10%, progress in precision medicine using CGP will increase the proportion of patients who receive treatment based on CGP and improve the prognosis of patients with pancreatic cancer.

In the era of genomic medicine, there is a growing need to obtain tissue samples suitable for tumor genotyping. Recent studies have focused on the development of optimal devices and techniques in endoscopic ultrasound-guided tissue acquisition (EUS-TA) for pancreatic cancer. In addition to sufficient tissue acquisition, it is also necessary to optimize preanalytical steps (e.g. sample processing, formalin fixation, and specimen preparation for analysis) to improve the success rate of gene panel testing. Close cooperation with pathologists and technicians is essential for successful analysis. However, in some cases, it is still challenging to obtain sufficient tissue samples. In such cases, we should consider other methods of genomic testing such as plasma cell-free DNA genotyping, microsatellite instability testing, and germline BRCA1/2 testing depending on the patient's condition. In this review, we discuss the role of EUS-TA in the clinical practice of gene panel testing for pancreatic cancer.

Genome sequencing using a liquid biopsy assay is an innovative technology for precision cancer medicine. Liquid biopsy assay for circulating tumor DNA is applied in the clinical setting, and clinical implementation as a comprehensive genomic profiling test is progressing in Japan. It is difficult to collect tumor samples for genome sequencing in patients with pancreatic cancer. Liquid biopsy is a useful technique in the field of precision medicine for pancreatic cancer. However, there are problems to be solved such as false negative results due to low sensitivity and false positive results due to clonal hematopoiesis of indeterminate potential compared to conventional genome sequencing using tumor samples. It also has some advantages in overcoming problems related to tumor heterogeneity reflecting genomic information of whole-body tumors, and allowing multiple sample collection due to its minimally invasive nature. Clinical application of liquid biopsy for early diagnosis, detection of minimal residual disease, monitoring for therapeutic effect and clonal evolution of tumor cells is highly anticipated for contributing to advances in the management of patients with pancreatic cancer.

"Genomic medicine" has two meanings depending on the purpose: ① assessing the risk of cancer development in individuals without cancer, aiming for early detection and preventive intervention, and ② finding effective treatments based on genetic information (Precision Medicine). As for ①, for the disease entity of familial pancreatic cancer, research on cancer predisposition genes or surveillance has been ongoing. As for ②, a phase III study (POLO trial) showed that Olaparib as maintenance therapy after treatment with a platinum-based regimen prolongs progression-free survival in patients harboring germline BRCA1/2 pathogenic variants. In addition, various oncogene panel tests and companion diagnostics have recently been clinically implemented which will lead to increasing the chances of detecting germline pathogenic variants, and development of infrastructure is important.

Early diagnosis of pancreatic cancer is essential to improve patients' prognosis. However, it is challenging to detect incipient lesions in the pancreas. Novel diagnostic methods have been developed recently, focusing on genomic and molecular alterations combined with radiological and endoscopic techniques. Detection of core molecules involved in the development of pancreatic cancer such as KRAS, TP53, SMAD4, and CDKN2A, and extracellular vesicles has been widely advocated. Digital PCR is expected to detect these mutations with higher sensitivity and at lower cost than next-generation sequencing and may be suitable as a pre-test for assessing the genomic alterations. In addition, comprehensive analysis of cancer genomics, including epigenetic alterations and expression of panels of non-coding RNAs related to the initiation of pancreatic tumorigenesis, is potentially pivotal for detecting distinct types of pancreatic cancer precursors. This review outlines genomic and molecular mechanisms underlying pancreatic carcinogenesis and introduces the latest technologies for the reliable detection of pancreatic tumors using accessible specimens, including body fluids.

Genome analyses of pancreatic ductal adenocarcinoma (PDAC) have revealed somatic mutations frequently in KRAS, TP53, SMAD4, and CDKN2A, as well as less frequently in ARID1A, ARID2, SMARCA4, KMT2C, KMT2D, KDM6A, RNF43, FAT1, FAT2, FAT3, FAT4, and TGFBR2. The only targetable KRAS mutation, KRAS G12C, has been identified in 2.6% of all KRAS mutations in patients with PDACs. Transcriptome analyses have revealed that PDACs can be classified into the classical type and the basal-like/squamous type, in which the latter is associated with a poorer prognosis than the former. Familial pancreatic cancer accounts for 7% of PDAC cases, and are likely to harbor deleterious germline mutations in APC, ATM, BRCA1, BRCA2, CHEK2, ERCC2, FANCA, FANCC, FANCE, FAT4, KMT2C, MLH1, MSH2, NF1, PALB2, POLE, RNF43, SMAD4, TP53, and TSC2. In the future, genome analyses of some specific cohorts or individuals with detailed clinical information may uncover more useful, clinically-oriented information that can make personalized medicine more efficient.

We report three patients with inferior pancreaticoduodenal artery (IPDA) aneurysm rupture. The patients include a 76-year-old man, a 53-year-old woman, and a 63-year-old man. In all patients, median arcuate ligament syndrome caused rupture of an IPDA aneurysm. With rapid diagnosis using contrast enhanced computed tomography scans, all patients were managed effectively with transcatheter arterial embolization (TAE) without delay. Two patients were complicated by duodenal stenosis due to retroperitoneal hematomas. Duodenal stenosis should be considered in patients with IPDA rupture. We propose careful resumption of oral intake after treatment.

A 40-year-old male was referred with a tumor in the tail of the pancreas incidentally found on a contrast-enhanced computed tomography (CT) scan, which showed a tumor enhanced mainly in the marginal area between the tail of the pancreas and the left adrenal grand. Magnetic resonance imaging revealed that the tumor had a high intensity signal inside and a low intensity signal in the marginal area in the T2 weighted images. The tissue intervening between the tail of the pancreas and the tumor was unclear, and it was thought to be a primary pancreatic tumor. Endoscopic ultrasonography (EUS) showed a hypoechoic mass with a well-defined border, a round shape, and a heterogenous interior area separate from the tail of the pancreas and the left adrenal grand. EUS-guided fine needle aspiration examination was performed, and he underwent laparoscopic distal pancreatectomy with a preoperative diagnosis of a pancreatic neuroendocrine tumor. The final diagnosis after pathological examination was a paraganglioma. Imaging findings of pancreatic neuroendocrine tumors and paragangliomas are similar and it is difficult to distinguish them. In the case of a tumor developing around the pancreas, careful consideration is required as to whether it is a primary pancreatic lesion or an extra-pancreatic lesion.