Pancreatic cancer is one of the cancers with very poor prognosis; there is an urgent need to identify novel biomarkers to improve its clinical outcomes. Circulating tumor DNA (ctDNA) from liquid biopsy has arisen as a promising biomarker for cancer detection and surveillance. However, it is known that the ctDNA detection rate in resected pancreatic cancer is low compared with other types of cancer. In this study, we collected paired tumor and plasma samples from 145 pancreatic cancer patients. Plasma samples were collected from 71 patients of treatment-naïve status and from 74 patients after neoadjuvant therapy (NAT). Genomic profiling of tumor DNA and plasma samples was conducted using targeted next-generation sequencing (NGS). Somatic mutations were detected in 85% (123/145) of tumors. ctDNA was detected in 39% (28/71) and 31% (23/74) of treatment-naïve and after-NAT groups, respectively, without referring to the information of tumor profiles. With a tumor-informed approach (TIA), ctDNA detection rate improved to 56% (40/71) and 36% (27/74) in treatment-naïve and after-NAT groups, respectively, with the detection rate significantly improved (p = 0.0165) among the treatment-naïve group compared to the after-NAT group. Cases who had detectable plasma ctDNA concordant to the corresponding tumor showed significantly shorter recurrence-free survival (RFS) (p = 0.0010). We demonstrated that TIA improves ctDNA detection rate in pancreatic cancer, and that ctDNA could be a potential prognostic biomarker for recurrence risk prediction

Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest cancer types. Activating oncogenic KRAS mutations are commonly observed in PDAC; however, oncogenic KRAS amplification is rarely observed, and its significance in prognosis and resistance to therapy remains poorly characterized. The present report describes the case of a 52‑year‑old male patient diagnosed with advanced PDAC with liver metastasis. The patient received modified FOLFIRINOX (mFFX) therapy to which the patient became intolerant with a strong inflammatory response. Subsequent treatment with gemcitabine plus nab‑paclitaxel failed to control the disease. Targeted genetic analysis revealed KRAS^G12D and TP53^R248Q mutations in the primary tumor and liver metastases. Analysis of circulating tumor DNA (ctDNA) before the first line of treatment confirmed these genetic findings and revealed a >4‑fold amplification of the mutant KRAS^G12D not detected in the primary tumor. Additionally, subsequent analysis confirmed a 5‑fold amplification of the KRASG12D allele in liver metastasis. Consecutive monitoring of ctDNA revealed an initial decrease in the tumor burden 2 weeks after the first cycle of mFFX. However, coinciding with treatment intolerance, a sharp increase in tumor mutational levels and KRAS^G12D amplification was observed 1 month later. The patient died 70 days after treatment initiation. Overall, amplification of oncogenic KRAS^G12D was not only associated with an aggressive phenotype, but also supported cancer resistance to chemotherapy. Importantly, this case suggests that plasma detection of KRAS^G12D amplification is feasible in the clinical routine and constitutes a powerful tool for assessing tumor aggressiveness.

Eosinophilic cholangiopathy (EC) presents with thickening and stenosis of the bile duct wall that is histologically characterized by eosinophil infiltration. The diagnosis is often difficult. We herein report a patient who had been followed up with a diagnosis of primary sclerosing cholangitis but had a final diagnosis of EC based on eosinophilia, histological findings of bile duct and liver biopsy specimens, and a review of a previous surgical specimen of the gallbladder. Antigen tests, isolation from her house, and accidental re-exposure to the antigen revealed that the causative antigen was the mite Dermatophagoides pteronyssinus.