Ryota Kiuchi

Pancreatic carcinoma mimicking diffuse-type autoimmune pancreatitis: important diagnostic role of pancreatic juice cytology using endoscopic naso-pancreatic drainage.

The occurrence of a diffusely swollen pancreas raises the possibility of several diseases in the differential diagnosis, including autoimmune pancreatitis (AIP), pancreatic lymphoma and whole pancreatic cancer (PC). Diffuse-type AIP, in particular, is characterized by a capsule-like rim, without dilation of the main pancreatic duct (MPD). In this article we report a case of PC that mimicked diffuse-type AIP on ultrasonography (US) and computed tomography (CT) images, which was successfully diagnosed by a cytology of pancreatic juice obtained using endoscopic naso-pancreatic drainage (ENPD).

Stearate-to-palmitate ratio modulates endoplasmic reticulum stress and cell apoptosis in non-B non-C hepatoma cells

The increased prevalence of hepatocellular carcinoma (HCC) without viral infection, namely, NHCC, is a major public health issue worldwide. NHCC is frequently derived from non‐alcoholic fatty liver (NAFL) and non‐alcoholic steatohepatitis, which exhibit dysregulated fatty acid (FA) metabolism. This raises the possibility that NHCC evolves intracellular machineries to adapt to dysregulated FA metabolism. We herein aim to identify NHCC‐specifically altered FA and key molecules to achieve the adaptation. To analyze FA, imaging mass spectrometry (IMS) was performed on 15 HCC specimens. The composition of saturated FA (SFA) in NHCC was altered from that in typical HCC. The stearate‐to‐palmitate ratio (SPR) was significantly increased in NHCC. Associated with the SPR increase, the ELOVL6 protein level was upregulated in NHCC. The knockdown of ELOVL6 reduced SPR, and enhanced endoplasmic reticulum stress, inducing apoptosis of Huh7 and HepG2 cells. In conclusion, NHCC appears to adapt to an FA‐rich environment by modulating SPR through ELOVL6.

Usefulness of four-dimensional flow-sensitive magnetic resonance imaging to evaluate hemodynamics in the pancreaticoduodenal artery

Pancreaticoduodenal artery (PDA) aneurysm associated with celiac axis compression by the median arcuate ligament (MAL) is a rare disorder, but may be lethal if ruptured. Therefore, prophylactic surgical treatments need to be considered when MAL compresses the celiac axis. We herein report the usefulness of an arterial flow analysis for objectively evaluating this pathophysiology under four-dimensional flow-sensitive magnetic resonance imaging (4D-flow MRI). Celiac artery stenosis was incidentally found under contrast-enhanced CT in a 50-year-old woman with symptomatic solitary pancreatic insulinoma. Under 4D-flow MRI, retrograde blood flow and aberrant wall shear stress were detected in the pancreaticoduodenal artery arcade. After obtaining informed consent, enucleation for insulinoma concomitant with MAL dissection was performed. Hypoglycemic attack completely resolved immediately after surgery. One month after surgery, 4D-flow MRI revealed normalized vectorial flow and wall shear stress in the PDA arcade without hypoglycemic attack. 4D-flow MRI is a very useful and non-invasive modality for objectively evaluating visceral artery hemodynamics.

Lethal Bleeding from a Duodenal Cancerous Ulcer Communicating with the Superior Mesenteric Artery in a Patient with Pancreatic Head Cancer

Pancreatic cancer often invades the duodenum and causes obstruction, but rarely causes massive duodenal bleeding. A 68-year-old male was admitted to our hospital because of vomiting. Enhanced abdominal CT showed a hypovascular tumor with air bubbles in the uncinate process of the pancreas. The tumor invaded the duodenum and metastasized to the liver and peritoneum. The main trunk of the superior mesenteric artery (SMA) was circumferentially involved. After admission, he had hematemesis and melena. Emergency gastroduodenoscopy revealed pulsating vessels in the third portion of the duodenum and he eventually experienced hemorrhagic shock. Severe bleeding occurred from his mouth and anus like a catastrophic flood. It was difficult to sustain blood pressure even with massive blood transfusion with pumping. After insertion of an intra-aortic balloon occlusion catheter, the massive bleeding was eventually stopped. Although we attempted interventional radiography, aortography revealed direct communication between the main SMA trunk and the duodenal lumen. The tumor was considered anatomically and oncologically unresectable. Thus, we did not perform further intervention. The patient died 2 h after angiography. Herein, we report the case of pancreatic head cancer causing lethal bleeding associated with tumor-involved SMA. Duodenal bleeding associated with pancreatic cancer invasion should be considered as an oncogenic emergency.

Abstract 2048: Saturated fatty acids in cell membrane phospholipids play an important role in chemoresistance in colorectal cancer

[Background and Aim] Resistance to chemotherapy represents the major obstacle to survival in patients with chemoresistant colorectal cancer. Various factors, such as drug efflux, autocrine survival signaling, and alterations in DNA damage repair mechanisms, can contribute to chemoresistance; however, the actual underlying mechanism is yet to be elucidated. The aim of this study was to elucidate the mechanism behind anticancer drug resistance based on lipidomics. [Materials and Methods] 1) Spheroids were derived from three colorectal cancer patient-derived xenograft models (A, B, and C) that were incubated with chemotherapeutic agents, such as 5-fluorouracil (5-FU). We analyzed the response rate of spheroids under 5-FU treatment. Global lipid analysis was performed on 5-FU resistance spheroids (A) and sensitive spheroids (C) using a Q Exactive LC-MS/MS mass spectrometer, and lipid identification was performed using the Lipid Search software. 2) We tried to identify genes that were responsible for changes in phospholipid profiles in the cell membrane. 3) To determine phospholipid profile changes in the cell membrane that occur in colon cancer cell lines (HCT116, SW480) during anticancer drug resistance, the genes responsible for such resistance were knocked down using siRNA. [Results and discussion] 1) Response to 5-FU was different in individual spheroids. Global lipid analysis and chemosensitivity assay revealed that phospholipids of 5-FU resistant spheroids were rich in saturated fatty acids (SFAs), while those of the 5-FU sensitive spheroids were rich in monounsaturated fatty acids (MUFAs). 2) The enzyme stearoyl-CoA desaturase (SCD) converts SFAs to MUFAs in the phospholipids. Based on these findings we hypothesized that decreased SCD expression is possibly associated with chemoresistance. 3) Cell lines with SCD knock down demonstrated increased SFA containing phospholipids and chemoresistance towards 5-FU. Viable cells after the administration of the anti-cancer agent confirmed that the expression of CD44 was upregulated. Therefore, changes in the phospholipid composition of cell membranes regulate 5-FU resistance in colon cancer. [Conclusions] Identification and analysis of the role of membrane lipids has become possible using high-sensitivity and high-resolution mass spectrometers and the relevant software, such as Lipid Search. Changes of phospholipid composition regulates chemoresistance. In future, investigation of the pathophysiology of membrane lipids in cancer may help to reveal novel strategies for cancer therapy. Citation Format: Takanori Hiraide, Takanori Sakaguchi, Satoru Furuhashi, Tomohiro Matsumoto, Yusuke Ozaki, Ryota Kiuchi, Makoto Takeda, Yasushi Shibasaki, Yoshifumi Morita, Hirotoshi Kikuchi, Megumi Baba, Mitsutoshi Setou, Hiroyuki Konno. Saturated fatty acids in cell membrane phospholipids play an important role in chemoresistance in colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2048. doi:10.1158/1538-7445.AM2017-2048