A Redox-Inactive Derivative of Tocotrienol Suppresses Tumor Growth of Mesothelioma Cells in a Xenograft Model.

Malignant mesothelioma (MM) is an aggressive cancer with poor prognosis. We focused on the anticancer activity of tocotrienol (T3) and have reported that a new redox-inactive T3 derivative (6-O-carboxypropyl-α-tocotrienol; T3E) exerts stronger inhibitory effects on MM cell growth than that of T3 in vitro. Furthermore, we have revealed some mechanisms of T3E that are involved in anti-MM effects. However, the effect of T3E in vivo remains unclear. In this study, we compared the plasma concentrations of T3E to that of T3 using mice to clarify differences in pharmacokinetics. Blood was sequentially collected after oral administration of T3 or T3E, and plasma concentrations were analyzed by HPLC. The area under the plasma T3 and T3E concentration-time curve from 0 to 24 h (AUC0-24 h) of T3E was two times higher than that of T3. In addition, we evaluated the effect of T3E oral administration on tumor growth using a xenograft model of mice that were transplanted with human MM cells (H2052 cell line). Tumor volume was significantly reduced without body weight loss in mice orally administered 150 mg/kg T3E once per 2 d for 10 d, which suggests that T3E has potential anti-MM effects.

Level of Fecal Calprotectin Correlates With Severity of Small Bowel Crohn's Disease, Measured by Balloon-assisted Enteroscopy and Computed Tomography Enterography.

BACKGROUND & AIMS: Previous studies have not found a correlation between fecal level of calprotectin and small bowel Crohn's disease (CD). However, these studies evaluated patients mainly by ileocolonoscopy, which views up to only the terminal ileum rather than entire small intestine. We investigated whether level of fecal calprotectin (FC) is a marker of active CD of the small bowel, identified by balloon-assisted enteroscopy and computed tomography enterography (CTE). METHODS: We performed a prospective study of 123 patients with CD (35 with ileitis, 72 with ileocolitis, and 16 with colitis) evaluated by balloon-assisted enteroscopy from May 2012 through July 2015 at Toho University Sakura Medical Centre in Japan. Patients with strictures detected by balloon-assisted enteroscopy were evaluated by CTE (n = 17). Fecal samples were collected from each patient, and levels of calprotectin were measured; patient demographic variables and medical history were also collected. We developed a CTE scoring system for disease severity that was based on bowel wall thickness, mural hyperenhancement, and engorged vasa recta. The association between level of FC and simple endoscopic index for CD score or CTE was evaluated by using Spearman rank correlation coefficient. RESULTS: Level of FC correlated with the simple endoscopic index for CD score (r = 0.6362, P < .0001), even in patients with only active disease of the small intestine (r = 0.6594, P = .0005). In the 17 patients with strictures that could not be passed with the enteroscope, CTE detected all lesions beyond the strictures as well as areas in the distal side of the strictures. Level of FC correlated with CTE score in these patients (r = 0.4018, P = .0011, n = 63). In receiver operating characteristic analyses, the FC cutoff value for mucosal healing was 215 µg/g; this cutoff value identified patients with healing with 82.8% sensitivity, 71.4% specificity, positive predictive value of 74.3%, negative predictive value of 80.6%, odds ratio of 12.0, and area under the receiver operating characteristic curve value of 0.81. CONCLUSIONS: A combination of measurement of level of FC and CTE appears to be effective for monitoring CD activity in patients with small intestinal CD, including patients with strictures that cannot be passed by conventional endoscopy.

Heterotopic Pancreas of the Jejunum Incidentally Detected by Preoperative Abdominal CT: Report of Two Cases and Review of the Literature.

Heterotopic pancreas (HP) is typically an asymptomatic malformation that can present anywhere along the gastrointestinal tract. It is often detected incidentally on surgery for other diseases or autopsy. We encountered 2 patients with jejunal HP incidentally detected by computed tomography (CT) performed for close evaluation of other diseases. In a 57-year-old woman diagnosed with reactive lymphoid hyperplasia on the dorsal portion of the pancreas head, CT detected a 15 mm oval-shaped submucosal lesion at the jejunum. In an 87-year-old woman diagnosed with type 2 adenocarcinoma occupying the sigmoid colon, CT detected a round-shaped submucosal tumor 15 mm in diameter in the jejunum. Both cases were histologically diagnosed as type 1 HP according to the classification by Heinrich. Contrast-enhanced CT revealed that the CT analyses of HP and pancreatic parenchyma were nearly identical in the arterial phase, but in the equilibrium phase, contrast enhancement persisted longer in HP than in the pancreatic parenchyma. There has been no report of asymptomatic jejunal HP preoperatively diagnosed by CT. These cases are presented with a review of the literature, particularly focusing on CT findings.