Michihiro Ono

Rapid on-site evaluation by endosonographer during endoscopic ultrasound-guided fine needle aspiration for pancreatic solid masses.

Endoscopic ultrasound‐guided fine needle aspiration (EUS‐FNA) is an established diagnostic method for patients with suspected pancreatic ductal carcinoma. Rapid on‐site evaluation (ROSE) has been reported to improve the accuracy. However, an on‐site cytopathologist is not routinely available in many institutions. One of the solutions may be ROSE by endosonographer. The aim was to examine whether diagnostic accuracy increases through ROSE by endosonographer using our cytological criteria.

Fucosylated TGF-β receptors transduces a signal for epithelial-mesenchymal transition in colorectal cancer cells.

Background:Transforming growth factor-β (TGF-β) is a major inducer of epithelial–mesenchymal transition (EMT) in different cell types. TGF-β-mediated EMT is thought to contribute to tumour cell spread and metastasis. Sialyl Lewis antigens synthesised by fucosyltransferase (FUT) 3 and FUT6 are highly expressed in patients with metastatic colorectal cancer (CRC) and are utilised as tumour markers for cancer detection and evaluation of treatment efficacy. However, the role of FUT3 and FUT6 in augmenting the malignant potential of CRC induced by TGF-β is unclear.Methods:Colorectal cancer cell lines were transfected with siRNAs for FUT3/6 and were examined by cell proliferation, invasion and migration assays. The expression and phosphorylation status of TGF-β downstream molecules were analysed by western blot. Fucosylation of TGF-β receptor (TβR) was examined by lectin blot analysis.Results:Inhibition of FUT3/6 expression by siRNAs suppressed the fucosylation of type I TβR and phosphorylation of the downstream molecules, thereby inhibiting the invasion and migration of CRC cells by EMT.Conclusion:Fucosyltransferase 3/6 has an essential role in cancer cell adhesion to endothelial cells by upregulation of sialyl Lewis antigens and also by enhancement of cancer cell migration through TGF-β-mediated EMT.

RNAi-mediated gene silencing of ST6GalNAc I suppresses the metastatic potential in gastric cancer cells

BackgroundST6GalNAc I is a sialyltransferase controlling the expression of sialyl-Tn antigen (STn), which is overexpressed in several epithelial cancers, including gastric cancer, and is highly correlated with cancer metastasis. However, the functional contribution of ST6GalNAc I to development or progression of gastric cancer remains unclear. In this study, we investigated the effects of suppression of ST6GalNAc I on gastric cancer in vitro and in vivo.MethodsGastric cancer cell lines were transfected with ST6GalNAc I siRNA and were examined by cell proliferation, migration, and invasion assays. We also evaluated the effect of ST6GalNAc I siRNA treatment in a peritoneal dissemination mouse model. The differences in mRNA levels of selected signaling molecules were analyzed by polymerase chain reaction (PCR) arrays associated with tumor metastasis in MKN45 cells. The signal transducer and activator of transcription 5b (STAT5b) signaling pathways that reportedly regulate the insulin-like growth factor-1 (IGF-1) were analyzed by Western blot.ResultsST6GalNAc I siRNA inhibited gastric cancer cell growth, migration, and invasion in vitro. Furthermore, intraperitoneal administration of ST6GalNAc I siRNA- liposome significantly inhibited peritoneal dissemination and prolonged the survival of xenograft model mice with peritoneal dissemination of gastric cancer. PCR array confirmed that suppression of ST6GalNAc I caused a significant reduction in expression of IGF-1 mRNA. Decreased IGF-1 expression in MKN45 cells treated with ST6GalNAc I siRNA was accompanied by reduced phosphorylation of STAT5b.ConclusionST6GalNAc I may regulate the gene expression of IGF-1 through STAT5b activation in gastric cancer cells and may be a potential target for treatment of metastasizing gastric cancer.

EUS-guided celiac plexus neurolysis by using highly viscous phenol-glycerol as a neurolytic agent (with video)

4 EUS-guided celiac plexus neurolysis (EUS-CPN) is considered to be a reliable treatment for cancer-related pain. However, inadequate distribution of the neurolytic agent to the celiac plexus (CP) has been presumed to contribute to the failure of pain relief. Indeed, it has been reported that the distribution of the neurolytic agent to only the left side of the celiac artery (CA) (as assessed by CT) is a significant predictor of negative response to EUSCPN. Generally, the injected neurolytic agent in EUS-CPN is more likely to flow into the left side of the CA. Further, it often spreads extensively beyond the CP and throughout the retroperitoneal cavity. These tendencies probably relate to the left lateral decubitus position during the procedure and the supine position after the procedure, which allow the neurolytic agent to spread extensively by gravity, preventing it from remaining near the CA. We hypothesized that a highly viscous neurolytic agent would remain around the CP and provide better pain relief. Ethanol and phenol are the neurolytic agents commonly used in CPN. Although they permanently destroy the CP, they have low viscosities. A representative highly viscous neurolytic agent is glycerol, which has been recommended

Phenol-based endoscopic ultrasound-guided celiac plexus neurolysis for East Asian alcohol-intolerant upper gastrointestinal cancer patients: A pilot study

AIM To investigate the effectiveness of phenol for the relief of cancer pain by endoscopic ultrasound-guided celiac plexus neurolysis (EUS-CPN). METHODS Twenty-two patients referred to our hospital with cancer pain from August 2009 to July 2011 for EUS-CPN were enrolled in this study. Phenol was used for 6 patients with alcohol intolerance and ethanol was used for 16 patients without alcohol intolerance. The primary endpoint was the positive response rate (pain score decreased to ≤ 3) on postoperative day 7. Secondary endpoints included the time to onset of pain relief, duration of pain relief, and complication rates. RESULTS There was no significant difference in the positive response rate on day 7. The rates were 83% and 69% in the phenol and ethanol groups, respectively. Regarding the time to onset of pain relief, in the phenol group, the median pre-treatment pain score was 5, whereas the post-treatment scores decreased to 1.5, 1.5, and 1.5 at 2, 8, and 24 h, respectively (P < 0.05). In the ethanol group, the median pre-treatment pain score was 5.5, whereas the post-treatment scores significantly decreased to 2.5, 2.5, and 2.5 at 2, 8, and 24 h, respectively (P < 0.01). There was no significant difference in the duration of pain relief between the phenol and ethanol groups. No significant difference was found in the rate of complications between the 2 groups; however, burning pain and inebriation occurred only in the ethanol group. CONCLUSION Phenol had similar pain-relieving effects to ethanol in EUS-CPN. Comparing the incidences of inebriation and burning pain, phenol may be superior to ethanol in EUS-CPN procedures.

Newly designed plastic stent for endoscopic placement above the sphincter of Oddi in patients with malignant hilar biliary obstruction

Plastic stent (PS) occlusion occurs as a result of bacterial adherence to the stents inner wall. To retain the bacteriological barrier, placing a PS above the sphincter of Oddi (‘inside stent’) has been investigated. We designed a new PS (inside stent with thread [IT] stent) with attachable nylon thread for use as an inside stent and for easy retrieval. The present study evaluated the IT stents technical feasibility and efficacy for malignant hilar biliary obstruction.

ENDOSCOPIC FINDINGS OF ENTEROPATHY‐TYPE T‐CELL LYMPHOMA BY DOUBLE‐BALLOON ENTEROSCOPY AND CAPSULE ENDOSCOPY

Enteropathy‐type T‐cell lymphoma (ETL) is a rare primary intestinal disorder, particularly in Japan, and there have been few reports on the endoscopic findings of the disease. Here we report detailed endoscopic findings of ETL based on double‐balloon enteroscopy and capsule endoscopy. Double‐balloon enteroscopy and capsule endoscopy may be useful tools for diagnosing and monitoring the effects of therapy in patients with ETL.

Pancreatic metastasis from a solitary fibrous tumor of the central nervous system.

CONTEXT Solitary fibrous tumor of the central nervous system is uncommon, with only around 200 reported cases. Further, extracranial metastasis is extremely rare, and only 5 cases of hematogenous metastases have been reported so far. To the best of our knowledge, there have been no reports of solitary fibrous tumor of the central nervous system metastasizing to the pancreas. CASE REPORT A 62-year-old woman was referred for evaluation of a pancreatic mass, which was strongly suspected to be a neuroendocrine tumor. However, the histological findings and immunohistochemical profile indicated the presence of a solitary fibrous tumor. Because the medical history revealed previous transcranial resection for intracranial meningioma 16 years ago, we conducted a pathological review of the brain specimen obtained by the first operation and found that it had the same histology and immunohistochemical profile as the current endoscopic ultrasound-guided fine-needle aspiration specimen. Consequently, the final diagnosis, on the basis of the brain specimen, was changed from meningioma to solitary fibrous tumor of the central nervous system, and the pancreatic mass was diagnosed as metastasis from solitary fibrous tumor of the central nervous system. The patient underwent middle pancreatectomy; the pancreatic specimen also had the same histology and immunohistochemical profile as the brain specimen. CONCLUSION Histological findings and immunohistochemical profile obtained by EUS-FNA are invaluable for the correct diagnosis to avoid excessive surgical procedures.

Relationship Between Increased Fucosylation and Metastatic Potential in Colorectal Cancer

BACKGROUND Fucose is utilized for the modification of different molecules involved in blood group determination, immunological reactions, and signal transduction pathways. We have recently reported that enhanced activity of the fucosyltransferase 3 and/or 6 promoted TGF-ß-mediated epithelial mesenchymal transition and was associated with increased metastatic potential of colorectal cancer (CRC), suggesting that fucose is required by CRC cells. With this in mind, we examined requirement of L-fucose in CRC cells and developed fucose-bound nanoparticles as vehicles for delivery of anticancer drugs specific to CRC. METHODS In this study, we first examined the expression of fucosylated proteins in 50 cases of CRC by immunochistochemical staining with biotinylated Aleuria aurantia lectin (AAL). Then we carried out an L-fucose uptake assay using three CRC cell lines. Finally, we developed fucose-bound nanoparticles as vehicles for the delivery of an anticancer drug, SN38, and examined tumor growth inhibition in mouse xenograft model (n = 6 mice per group). All statistical tests were two-sided. RESULTS We found a statistically significant relationship between vascular invasion, clinical stage, and intensity score of AAL staining (P≤ .02). L-fucose uptake assay revealed that L-fucose incorporation, as well as fucosylated protein release, was high in cells rich in fucosylated proteins. L-fucose-bound liposomes effectively delivered Cy5.5 into CRC cells. The excess of L-fucose decreased the efficiency of Cy5.5 uptake through L-fucose-bound liposomes, suggesting an L-fucose receptor dependency. Intravenously injected, L-fucose-bound liposomes carrying SN38 were successfully delivered to CRC cells, mediating efficient tumor growth inhibition (relative tumor growth ratio: no treatment group [NT], 8.29 ± 3.09; SN38-treated group [SN38], 3.53 ± 1.47; liposome-carrying, SN38-treated group [F0], 3.1 ± 1.39; L-fucose-bound, liposome-carrying, SN38-treated group [F50], 0.94 ± 0.89; F50 vs NT,P= .003; F50 vs SN38,P= .02, F50 vs F0,P= .04), as well as prolonging survival of mouse xenograft models (log-rank test,P< .001). CONCLUSIONS Thus, fucose-bound liposomes carrying anticancer drugs provide a new strategy for the treatment of CRC patients.

A Prospective Multicenter Study Evaluating Bleeding Risk after Endoscopic Ultrasound-Guided Fine Needle Aspiration in Patients Prescribed Antithrombotic Agents

Background/Aims Although the risk of bleeding after endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is low, the safety of EUS-FNA in patients prescribed antithrom-botic agents is unclear. Therefore, this study evaluated the incidence of bleeding after EUS-FNA in those patients. Methods Between September 2012 and September 2015, patients who were prescribed antithrombotic agents underwent EUS-FNA at 13 institutions in Japan were prospectively enrolled in the study. The antithrombotic agents were managed according to the guidelines of the Japanese Gastrointestinal Endoscopy Society. The rate of bleeding events, thromboembolic events and other complications within 2 weeks after EUS-FNA were analyzed. Results Of the 2,629 patients who underwent EUS-FNA during the study period, 85 (62 males; median age, 74 years) patients were included in this stduy. Two patients (2.4%; 95% confidence interval [CI], 0.6% to 8.3%) experienced bleeding events. One patient required surgical intervention for hemothorax 5 hours after EUS-FNA, and the other experienced melena 8 days after EUS-FNA and required red blood cell transfusions. No thromboembolic events occurred (0%; 95% CI, 0.0% to 4.4%). Three patients (3.5%; 95% CI, 1.2% to 10.0%) experienced peri-puncture abscess formation. Conclusions The rate of bleeding after EUS-FNA in patients prescribed antithrombotic agents might be considerable.