Duodenal stenting followed by systemic chemotherapy for patients with pancreatic cancer and gastric outlet obstruction.

OBJECTIVES: Endoscopic duodenal stenting has recently been proposed as a substitute for surgical gastrojejunostomy for the treatment of gastric outlet obstruction. We aimed to evaluate the efficacy and safety of duodenal stenting followed by systemic chemotherapy for patients with advanced pancreatic cancer with gastric outlet obstruction. METHODS: This was a single-center, retrospective cohort study, conducted at an academic medical center, of 71 patients with advanced pancreatic cancer and gastric outlet obstruction (mean age: 67.6 years; range: 31-92 years) who underwent duodenal stenting with or without subsequent chemotherapy. Overall survival, duration of oral intake of foods, the rate of introduction of chemotherapy, progression-free survival, and adverse events were evaluated. RESULTS: Stent placement was technically successful in 69 (97%) patients. Thirty-six (51%) patients were treated with chemotherapy: 17 with gemcitabine alone, 15 with S-1 alone, 3 with FOLFIRINOX, and 1 with paclitaxel. Median progression-free survival and overall survival after chemotherapy were 2.6 months (95% confidence interval: 1.3-3.9 months) and 4.7 months (95% confidence interval: 2.6-6.8 months), respectively. Cases of grade 3 anemia were frequently observed during chemotherapies following duodenal stenting (32%). Tumor stage, performance status, neutrophil-to-lymphocyte ratio, and introduction of chemotherapy were independent prognostic factors for survival (hazard ratios of 3.73, 2.21, 2.69, and 1.85 with p-values of <0.001, 0.010, <0.001, and 0.045, respectively). CONCLUSIONS: The findings of this study suggest that endoscopic duodenal stenting is an advantageous treatment in advanced pancreatic cancer patients with gastric outlet obstruction regarding its safety and smooth conduction of subsequent chemotherapies.

Development of p-carborane-based nonsteroidal progesterone receptor antagonists.

Progesterone receptor (PR) regulates various physiological processes, including the female reproductive system, and development of nonsteroidal PR antagonists is considered desirable for clinical application, as they are expected to have reduced side effects. We have synthesized a series of nonsteroidal PR antagonists using a 4-cyanophenyl-p-carborane core structure. Among them, compound 14d exhibited potent PR-antagonistic activity (IC50: 27 nM). It showed high binding affinity for PR, but did not bind to androgen receptor or estrogen receptor. This PR-selective antagonist may be a promising lead compound for clinically applicable progesterone receptor modulators.

Endoscopic submucosal dissection (two-point fixed ESD) for early esophageal cancer.

BACKGROUND: We have been attempting to improve the safety, reliability and simplicity of endoscopic submucosal dissection for the treatment of early esophageal cancer and to shorten the time needed for this operation. METHODS: The present study involved nine patients with well-differentiated intramucosal early esophageal cancer over 20 mm in diameter. Two-point fixed endoscopic submucosal dissection was carried out. RESULTS: In all nine cases, the mucosal area to be dissected was successfully identified and kept under direct vision, allowing two-point fixation of the mucosa with forceps and the hood during adequate counter-traction. In this way, the respiration-caused movement of submucosal tissue between the two fixing points was suppressed almost completely. Hemostasis and manipulation on blood vessels were easy with this procedure and dissection could be completed safely, without causing perforation. CONCLUSION: Endoscopic submucosal dissection with a transparent hood fitted with a mucosa-holding forceps channel is highly useful, safe and simple when applied to the esophagus.

New choke diseases and their molecular phylogenetic analysis in Agropyron ciliare var. minus and Agropyron tsukushiense var. transiens.

Choke diseases were surveyed in two closely related grass species, Agropyron ciliare var. minus and Agropyron tsukushiense var. transiens, in Shiga Prefecture, Japan. Perithecia and ascospores were not observed in either case. Stromata on A. ciliare var. minus enclosed and sterilized young inflorescences, as in the typical choke symptoms by Epichloë typhina. On the other hand stromata on A. tsukusiense var. transiens thinly covered mature spikes with white epiphyllous hyphae, as in stromata of Ephelis spp. The fungal isolates produced typical Neotyphodium-type conidia. Molecular phylogenetic analyses using the beta-tubulin gene (tubB) indicated that the two Agropyron species are infected with the species grouping into a novel single clade among Epichloë species and they are closely related to a haploid of hybrid Neotyphodium species. The host plant features may be the cause of the differences between stromata of A. ciliare var. minus and A. tsukushiense var.