Background: The guidewire (GW) plays an important role in pancreatobiliary endoscopy. GW quality is a critical factor in the effectiveness and efficiency of pancreatobiliary endoscopy. In this study, we evaluate a new 0.025 inch multipurpose endoscopic GW: the M-Through. Methods: Our study was a multicenter retrospective analysis. We enrolled patients who underwent endoscopic procedures using the M-Through between May 2018 and April 2020. Patients receiving the following endoscopic treatments were enrolled: common bile duct (CBD) stone extraction, endoscopic drainage for distal and hilar malignant biliary obstruction (MBO), and endoscopic drainage for acute cholecystitis. For each procedure, we examined the rate of success without GW exchange. Results: A total of 170 patients (80 with CBD stones, 60 with MBO, and 30 with cholecystitis) were enrolled. The rate of completion without GW exchange was 100% for CBD stone extraction, 83.3% for endoscopic drainage for MBO, and 43.3% for endoscopic drainage for cholecystitis. In unsuccessful cholecystitis cases with the original GW manipulator, 1 of 8 cases succeeded in the manipulator exchange. Including 6 cases who changed GW after the manipulator exchange, 11 of 16 cases succeeded in changing GW. There was significant difference in the success rate between the manipulator exchange and GW exchange (p = 0.03). The insertion of devices and stent placement after biliary cannulation (regardless of type) were almost completed with M-through. We observed no intraoperative GW-related adverse events such as perforation and bleeding due to manipulation. Conclusion: The 0.025 inch M-Through can be used for endoscopic retrograde cholangiopancreatography-related procedures efficiently and safely. Our study found high rates of success without GW exchange in all procedures except for endoscopic drainage for cholecystitis. This GW is considered (1) excellent for supportability of device insertion to remove CBD stones; (2) good for seeking the biliary malignant stricture but sometimes need the help of a hydrophilic GW; (3) suboptimal for gallbladder drainage that require a high level of seeking ability.

Cell-free DNA (cfDNA) shed from tumors into the circulation offers a tool for cancer detection. Here, we evaluated the feasibility of cfDNA measurement and utility of digital PCR (dPCR)-based assays, which reduce subsampling error, for diagnosing pancreatic ductal adenocarcinoma (PDA) and surveillance of intraductal papillary mucinous neoplasm (IPMN). We collected plasma from seven institutions for cfDNA measurements. Hot-spot mutations in KRAS and GNAS in the cfDNA from patients with PDA (n = 96), undergoing surveillance for IPMN (n = 112), and normal controls (n = 76) were evaluated using pre-amplification dPCR. Upon Qubit measurement and copy number assessment of hemoglobin-subunit (HBB) and mitochondrially encoded NADH:ubiquinone oxidoreductase core subunit 1 (MT-ND1) in plasma cfDNA, HBB offered the best resolution between patients with PDA relative to healthy subjects [area under the curve (AUC) 0.862], whereas MT-ND1 revealed significant differences between IPMN and controls (AUC 0.851). DPCR utilizing pre-amplification cfDNA afforded accurate tumor-derived mutant KRAS detection in plasma in resectable PDA (AUC 0.861–0.876) and improved post-resection recurrence prediction [hazard ratio (HR) 3.179, 95% confidence interval (CI) 1.025–9.859] over that for the marker CA19-9 (HR 1.464; 95% CI 0.674–3.181). Capturing KRAS and GNAS could also provide genetic evidence in patients with IPMN-associated PDA and undergoing pancreatic surveillance. Plasma cfDNA quantification by distinct measurements is useful to predict tumor burden. Through appropriate methods, dPCR-mediated mutation detection in patients with localized PDA and IPMN likely to progress to invasive carcinoma is feasible and complements conventional biomarkers.

Background Pancreatic cancer is a refractory malignancy, and the development of a new effective treatment strategy is needed. We generated a dendritic cell vaccine by culturing monocytes obtained by apheresis of blood from each patient, inducing their differentiation into dendritic cells, and pulsing with tumor antigen peptides. However, the clinical efficacy of the vaccine has not been established. We therefore decided to conduct an exploratory clinical trial of dendritic cell vaccine loaded with Wilms’ tumor gene 1 peptides (TLP0-001) as a potential new treatment for patients with advanced pancreatic cancer refractory to standard chemotherapy. Methods This is an investigator-initiated, double-blind, comparative trial. The patients were allocated to two groups in a 1:1 ratio through a central registration by dynamic allocation. A total of 185 patients with inoperable or metastatic pancreatic cancer who were refractory or intolerant to standard primary chemotherapy with gemcitabine plus nab-paclitaxel will be allocated to secondary treatment either with placebo in combination with S-1 (the control group) or TLP0-001 in combination with S-1 (the investigational product group). The primary objective of this trial is to evaluate the safety and efficacy (as measured by overall survival) of the investigational product by comparing the two groups. This clinical trial will be performed in accordance with Japanese Good Clinical Practice guidelines. Discussion Clinical trials of the standard regimen, including gemcitabine, for advanced pancreatic cancer are ongoing worldwide. However, a strategy for after the primary treatment has not been established. We therefore decided to conduct this study to evaluate the safety and efficacy of TLP0-001 as a secondary treatment for pancreatic cancer in anticipation of the approval of this new drug in Japan. This trial is conducted with full consideration of safety, as it is the first-in-human clinical trial of TLP0-001; thus, the trial will be conducted only at the Second Department of Surgery at Wakayama Medical University until the safety is confirmed by interim analysis. We plan to conduct a multicenter trial at 18 institutions in Japan after confirmation of the safety. Trial registration University Hospital Medical Information Network Clinical Trials Registry, UMIN000027179 . Registered on 9 April 2017.

Portal vein thrombosis (PVT) is one of the most critical disorders in liver disease patients. These patients have the imbalance of coagulation and coagulation inhibition resulting from decreased levels of coagulation inhibitory factors, such as protein C, protein S, and antithrombin III (AT‐III). We designed this randomized, double‐blind, placebo‐controlled trial comparing the safety and efficacy of AT‐III for PVT in liver disease patients with those who received no treatment.

Genetic alterations responsible for the initiation of cancer may serve as immediate biomarkers for early diagnosis. Plasma levels of cell‐free DNA (cfDNA) in patients with cancer are higher than those in healthy individuals; however, the major technical challenge for the widespread implementation of cfDNA genotyping as a diagnostic tool is the insufficient sensitivity and specificity of detecting early‐stage tumors that shed low amounts of cfDNA. To establish a protocol for ultrasensitive droplet digital polymerase chain reaction (ddPCR) for quantification of low‐frequency alleles within a limited cfDNA pool, two‐step multiplex ddPCR targeting eight clinically relevant mutant KRAS variants was examined. Plasma samples from patients with colorectal (n = 10) and pancreatic cancer (n = 9) were evaluated, and cfDNA from healthy volunteers (n = 50) was utilized to calculate reference intervals. Limited cfDNA yields in patients with resectable colorectal and pancreatic cancers did not meet the requirement for efficient capture and quantification of rate mutant alleles by ddPCR. Eight preamplification cycles followed by a second‐run ddPCR were sufficient to obtain approximately 5000–10 000 amplified copies per ng of cfDNA, resolving the subsampling issue. Furthermore, the signal‐to‐noise ratio for rare mutant alleles against the extensive background presented by the wild‐type allele was significantly enhanced. The cutoff limit of reference intervals for mutant KRAS was determined to be ~ 0.09% based on samples from healthy individuals. The modification introduced in the ddPCR protocol facilitated the quantification of low‐copy alleles carrying driver mutations, such as oncogenic KRAS, in localized and early‐stage cancers using small blood volumes, thus offering a minimally invasive modality for timely diagnosis.

TPS464 Background: Pancreatic ductal adenocarcinoma (PDA) is still a dismal disease, and there is an urgent need to establish novel tool for early diagnosis of the tumor. There are two main types of pathologically and genetically distinct precursors for PDA — pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary mucinous neoplasia (IPMN). Non-invasive markers for these precursor lesions have the potential to predict subsequent invasive tumor. Methods: Circulating cell-free DNA (cfDNA) released from tumor cells into the blood has been intensively studied as a novel way to monitor the genetic changes. To detect the cfDNA representing for the initiation and progression of PDA could be of the candidate for them. The role of cfDNA genotyping targeting the major driver mutations in these precursors, such as KRAS and GNAS, are currently under investigation in Japanese patients who have pancreatic tumors (UMIN000012810). The major technical challenge is to specifically detect the small fraction of tumor-derived DNA in patient plasma and urine. Since sequencing of target mutant alleles in cfDNA has a limitation to detect very low frequency variants, we sought to establish protocols for super-sensitive and absolute quantification of the “key drivers” for pancreatic tumor using a droplet digital PCR platform (Bio-Rad; QX200). The primary endpoint of this multi-center prospective analysis is to evaluate whether such an approach can appropriately monitor the risk of IPMN progression and detect localized early-stage PDA. Thirty cases of PDA and 90 cases of IPMN have been enrolled thus far. Detailed protocol for the study and improved technical points to quantify low-frequency variants will be discussed.

There are three types of pancreatic neoplasms that predominantly have an intraductal growth pattern: the common, usually cystic, intraductal papillary mucinous neoplasms (IPMNs); the rare, usually solid intraductal tubulopapillary neoplasms (ITPNs); and the rare intraductal tubular pyloric gland-type adenoma. In addition to these three tumor types, pancreatic neoplasms with a usually solid growth pattern such as acinar cell carcinomas, neuroendocrine tumors, and undifferentiated carcinomas may present, though very rarely, as predominantly intraductally growing neoplasms. IPMNs can be subclassified into main duct and branch duct tumors; into low- and high-grade dysplasia groups; and into tumors with intestinal, pancreatobiliary, oncocytic, or gastric cellular differentiation. The intestinal-, pancreatobiliary-, and oncocytic-type IPMNs occur predominantly in the main duct of the head of the pancreas and more commonly progress to invasive adenocarcinomas. The gastric-type IPMNs are frequently multifocal, occur predominantly in the branch ducts of the uncinate process, and have a low risk of progressing to invasive carcinoma. The prognosis for patients with an IPMN depends largely on the subtype and the presence and the stage of an invasive carcinoma. ITPNs are nodular tumors, often in the pancreatic head, and composed of densely packed tubular glands. Molecular genetics reveal KRAS, GNAS, and RNF43 as the most frequently mutated genes in IPMNs, while ITPNs show wild-type KRAS. Recent progress in genetic sequencing of pancreatic neoplasms and the identification of specific genetic mutations also holds promise for the future development of novel gene-based diagnostic tests in intraductal neoplasms of the pancreas that might even be used in preoperative conditions.

We previously developed an immunotherapy treatment utilizing a cancer vaccine reagent KIF20A-66 in order to treat pancreatic cancer. KIF20A-66 is HLA-A24-restricted epitope peptide derived from KIF20A, a member of kinesin super family protein 20A that is significantly transactivated in pancreatic cancer. In this report, we further demonstrated non-randomized, open-label, single centered phase I/II clinical trial of immunotherapy using the KIF20A-66 peptide for the patients with advanced pancreatic cancer.

We reviewed the efficacy and complications of transcatheter arterial chemoembolization using degradable starch microspheres (DSM) for primary neuroendocrine tumors of the liver or liver metastases from gastrointestinal neuroendocrine tumors in ten patients. The rate of complete and partial response was 70.0%. The one year and two year survival rate was 77.8% respectively, with a median survival time of 852 days (28.4 months). All symptoms and laboratory data related to treatment were acceptable. It is thought that DSM-TACE is an effective treatment for inoperable liver neuroendocrine tumors or liver metastases from gastrointestinal neuroendocrine tumors.

A 51-year-old woman who had undergone gastrectomy for advanced gastric cancer was found to have a splenic tumor during the postoperative clinical observation. Abdominal computed tomography (CT) demonstrated solitary splenic tumor 15mm in diameter with delayed contrast enhancement. Abdominal ultrasonography (US) revealed low echoic mass with enhancement at vascular and perfusion image. We performed splenectomy to exclude the possibility of the metastatic tumor. The tumor was histopathologically diagnosed as inflammatory pseudotumor because of the presence of acidophilic fiber proliferation, hyalinized tissue and infiltration of lymphocytes and plasma cells.

We reviewed the effects and complications of transcatheter arterial chemoembolization (TACE), using degradable starch microspheres (DSM) in eight patients with hepatic metastases from gastric cancer. The rate of complete remission (CR) +partial remission (PR) was 62.5%, and the actual survival rates at one and two years post-treatment were 87.5%, and 52.5% respectively. The median survival time was 36.1 months. Almost all side effects were acceptable but in one case, we observed liver abscess. From this study, we suggest that DSM-TACE might be a safe and effective multimodal treatment for metastatic liver tumors in patients with gastric cancer.

We describe a case of initially unresectable locally advanced intrahepatic cholangiocarcinoma that showed remarkable regression after transcatheter arterial chemoembolization with degradable starch microspheres, allowing for subsequent successful curative resection. A 75-year-old female was referred to our hospital with a large hepatic mass. Computerized tomography examination showed a huge mass in the right liver extended partially to the left liver. Intrahepatic cholangiocarcinoma was strongly suspected, but surgical resection was abandoned due to the local spread in the liver. Three courses of transcatheter arterial chemoembolization with degradable starch microspheres were performed. The anticancer agents, mitomycin C and epirubicin, combined with degradable starch microspheres were injected from the catheter for chemoembolization. After three courses of transcatheter arterial chemoembolization, the tumor size decreased from 10cm to 5.5cm in diameter. Then right trisegmentectomy together with extra-hepatic bile duct excision was performed. At 25 months after the first therapy and 21 months after operation, the patient remains healthy without recurrence. Transcatheter arterial chemotherapy with degradable starch microspheres may be a treatment of choice with locally advanced intrahepatic cholangiocarcinoma.

A 66-year-old male with multiple liver tumors was diagnosed as having malignant carcinoid. The case exhibited carcinoid syndrome with wheezing and high urine 5-Hydroxy-Indole Acetic Acid and serum serotonin concentrations. A search for the primary lesion failed to detect tumors except those in the liver, leading to the diagnosis of primary hepatic carcinoid. Repeated transcatheter arterial chemoembolization with degradable starch microspheres decreased the tumors in size and improved the subjective symptoms. Transcatheter arterial chemoembolization with degradable starch microspheres is a useful treatment for unresectable malignant carcinoid of liver origin.

A 60-year-old female was found to have high serum amylase concentrations at a medical check-up. Dynamic computed tomography and magnetic resonance imaging demonstrated a mass in the body of the pancreas, which was enhanced in the late phase of the scans by administration of a contrast medium. Endoscopic retrograde pancreatography showed a stenosis of the main pancreatic duct at the body, and brushing cytology from the region revealed adenocarcinoma. Distal pancreatectomy was performed. The tumor was a well-differentiated adenocarcinoma, measuring 15 x l0 mm. Fibrous tissues were sparsely distributed in the tumor, and there was an increase of dilated veins, in particular at the margin. Late-phase enhancement of the tumor with computed tomography or magnetic resonance imaging was considered to be correlated with this abundant vascular structure in the tumor. Marked tumor enhancement in the late phase might be a characteristic finding suggesting an early-stage pancreatic adenocarcinoma, which should be carefully checked.

Degradable starch microspheres（DSM）は，肝動脈から投与した場合，約1時間血流を停滞させる．この間，DSMと一緒に投与された薬剤の腫瘍への集積は，たんなる動注の場合よりも増大し，さらに周囲正常肝組織への集積の数倍になる．これらの特性から，転移性肝がんに対して有効性が確認され，現在DSMは転移性肝がん治療に保険適応となっている．筆者らの検討では肝細胞がん，特に血管浸潤などを伴う進行肝細胞がんに対しても有効であることがわかった．塞栓効果が一過性であることから，治療後の肝機能障害は軽度であり，肝機能障害の強い肝悪性腫瘍の治療に，これまでの動脈化学塞栓療法より安心して施行することが出来る．

nous system shunt was visualized as cystic lesions with dilatation of hepatic or portal vein branch by ultrasonography.Color doppler ultrasonography can easly confirm blood flow and communication of aneurysm and vessels.IHPVA is not always related with portal hypertension and its clinical significance remains still unknown.