Makoto Natsume

Maltotriose Conjugation to a Chlorin Derivative Enhances the Antitumor Effects of Photodynamic Therapy in Peritoneal Dissemination of Pancreatic Cancer

Peritoneal dissemination is a major clinical issue associated with dismal prognosis and poor quality of life for patients with pancreatic cancer; however, no effective treatment strategies have been established. Herein, we evaluated the effects of photodynamic therapy (PDT) with maltotriose-conjugated chlorin (Mal3-chlorin) in culture and in a peritoneal disseminated mice model of pancreatic cancer. The Mal3-chlorin was prepared as a water-soluble chlorin derivative conjugated with four Mal3 molecules to improve cancer selectivity. In vitro, Mal3-chlorin showed superior uptake into pancreatic cancer cells compared with talaporfin, which is clinically used. Moreover, the strong cytotoxic effects of PDT with Mal3-chlorin occurred via apoptosis and reactive oxygen species generation, whereas Mal3-chlorin alone did not cause any cytotoxicity in pancreatic cancer cells. Notably, using a peritoneal disseminated mice model, we demonstrated that Mal3-chlorin accumulated in xenograft tumors and suppressed both tumor growth and ascites formation with PDT. Furthermore, PDT with Mal3-chlorin induced robust apoptosis in peritoneal disseminated tumors, as indicated by immunohistochemistry. Taken together, these findings implicate Mal3-chlorin as a potential next-generation photosensitizer for PDT and the basis of a new strategy for managing peritoneal dissemination of pancreatic cancer. Mol Cancer Ther; 16(6); 1124–32. ©2017 AACR.

Predictors of stent dysfunction after self-expandable metal stent placement for malignant gastric outlet obstruction: tumor ingrowth in uncovered stents and migration of covered stents

BackgroundEndoscopic metallic stenting is widely accepted as a palliation therapy for malignant gastric outlet obstruction (GOO). However, the predictors of stent dysfunction have not been clarified. We aimed to evaluate the predictors, especially tumor ingrowth in uncovered self-expandable metallic stents (U-SEMS) and migration of covered self-expandable metallic stents (C-SEMS), which are the main causes related to the stent characteristics.MethodsIn this multicenter retrospective study, we compared patients with U-SEMS and C-SEMS in terms of clinical outcomes, and predictors of stent dysfunction.ResultsIn total, 252 patients (126 with U-SEMS and 126 with C-SEMS) were enrolled. There were no significant differences in technical success, clinical success, GOO score, or time to stent dysfunction. Tumor ingrowth was significantly more frequent in U-SEMS (U-SEMS, 11.90% vs. C-SEMS, 0.79%; p = 0.002), and stent migration was significantly more frequent for C-SEMS (C-SEMS, 8.73% vs. U-SEMS, 0.79%; p = 0.005). Karnofsky performance status (p = 0.04), no presence of ascites (p = 0.02), and insufficient (<30%) stent expansion (p = 0.003) were significantly associated with tumor ingrowth in U-SEMS. Meanwhile, a shorter stent length (p = 0.05) and chemotherapy (p = 0.03) were predictors of C-SEMS migration.ConclusionsBoth U-SEMS and C-SEMS are effective with comparable patencies. Tumor ingrowth and stent migration are the main causes of stent dysfunction for U-SEMS and C-SEMS, respectively. With regard to stent dysfunction, U-SEMS might be a good option for patients receiving chemotherapy, while C-SEMS with longer stents for patients in good condition. (Clinical trial registration number: UMIN000024059).

Novel characteristics of traction force in biliary self-expandable metallic stents

In recent years, knowledge concerning the mechanical properties of self‐expandable metallic stents (SEMS) has increased. In a previous study, we defined traction force and traction momentum and reported that these characteristics are important for optimal stent deployment. However, traction force and traction momentum were represented as relative values and were not evaluated in various conditions. The purpose of the present study was to measure traction force in various situations assumed during SEMS placement.

Case of pancreatic metastasis from colon cancer in which cell block using the Trefle® endoscopic scraper enables differential diagnosis from pancreatic cancer

Endoscopic transpapillary brush cytology and forceps biopsy during endoscopic retrograde cholangiopancreatology are generally used to obtain pathological evidence of biliary strictures. Recently, the new endoscopic scraper Trefle® has been reported and demonstrated high cancer detectability in malignant biliary strictures. This device is used to scrape the stricture over the guidewire, and, in the original method, the tissue and/or cell samples obtained are subjected to histological and/or cytological analysis separately. However, discrimination of chunks of tissue is hampered by the opacity of the surrounding fluid. We have developed a cell block technique for the Trefle® device without dividing obtained specimens into tissue and cellular components, which is the simplest method and enables immunohistochemical analysis. We present a case of obstructive jaundice diagnosed immunohistochemically as pancreatic metastasis from colon cancer using cell block sections obtained with the Trefle® device, which procedure is as easy as conventional brush cytology.

Autoimmune Hemolytic Anemia Obscured by the Obstructive Jaundice Associated with IgG4-related Sclerosing Cholangitis in a Patient with Type 1 Autoimmune Pancreatitis: A Case Report and Review of the Literature

Type 1 autoimmune pancreatitis (AIP) is a pancreatic manifestation of IgG4-retated disease that is often associated with IgG4-related sclerosing cholangitis (IgG4-SC). Autoimmune hemolytic anemia (AIHA) is an immune-related disease that causes hemolytic anemia. Although type 1 AIP/IgG4-SC and AIHA have a shared etiology as a presumed autoimmune disease, they rarely overlap, and their association has not been clarified. Secondary AIHA might not be diagnosed appropriately because the obstructive jaundice observed in type 1 AIP/IgG4-SC can obscure the presence of hemolytic jaundice. We herein report a case of type 1 AIP/IgG4-SC overlapping with secondary AIHA along with a review of the literature.