Randomized Phase II trial of paclitaxel plus valproic acid vs paclitaxel alone as second-line therapy for patients with advanced gastric cancer

The standard regimen of second-line chemotherapy for patients with unresectable gastric cancer has not been established. However, weekly paclitaxel (wPTX) has become the preferable second-line chemotherapy in Japan. Histone deacetylase (HDAC) inhibitors have been shown to have antiproliferative activity through cell-cycle arrest, differentiation, and apoptosis in gastric cancer cells. One HDAC inhibitor, valproic acid (VPA), also inhibits tumor growth by inducing apoptosis, and enhances the efficacy of paclitaxel in a mouse xenograft model of gastric cancer. wPTX plus VPA as a second-line chemotherapy is expected to improve survival in gastric cancer patients. A multicenter randomized Phase II study was conducted to compare the effects of wPTX plus VPA and wPTX alone. A total of 66 patients participated in this study. The primary end point of the study was overall survival, and secondary end points were progression-free survival, response rate, and assessment of peripheral neuropathy. © 2015 Fushida et al

Clinicopathological Parameters Associated with Surgical Site Infections in Patients who Underwent Pancreatic Resection

Background/Aims: To clarify parameters associated with postoperative surgical site infection (SSI) after pancreatectomy, we examined clinicopathological and surgical records in 186 patients who underwent pancreatectomy at a single academic institute. Methodology: Patient demographics, liver functional parameters, histological findings, surgical records and post-hepatectomy outcomes during hospitalization were compared between the non-SSI and SSI group, in which SSIs included superficial and deep SSIs. Results: The prevalence of SSI (29-35%) has not changed over an 18-year period. With respect to patient demographics and laboratory data, no parameters were associated with postoperative SSI. In surgical records, the operating time in the SSI group tended to be longer in comparison with that in the non-SSI group (618 vs. 553 minutes, respectively) but not significantly different (p=0.070). With respect to postoperative outcomes, time to oral intake in the SSI group was significantly longer than that in the non-SSI group (21.2 vs. 13.7 days, respectively) (p<0.01). Incidences of pancreatic fistula, postoperative bleeding, long-term ascites and re-operation were significantly more frequent in the SSI group in comparison with the non-SSI group (p<0.05). Decrease of body weight after surgery in the SSI group was significantly greater than that in the non-SSI group (-4.1 vs. -2.7kg, respectively) (p<0.05). Period of hospital stay in the SSI group was significantly longer than that in the non-SSI group (37 vs. 25 days) (p<0.05). Multivariate analysis showed that only postoperative pancreatic fistula was significantly associated with SSI (p<0.01). Conclusions: SSI is an important risk factor of longer hospital stay after pancreatectomy and prevention of pancreatic fistula through the future improvement of surgical procedures is necessary to decrease SSI rates

Evaluation of the efficacy of palonosetron for prevention of chemotherapy-induced nausea and vomiting in patients with gastric cancer treated with S-1 plus cisplatin

our previous study, which used granisetron, aprepitant, and dexamethasone, to assess the relative effectiveness of palonosetron versus granisetron in combination antiemetic therapy. Results Of the 72 included patients, 66 (91.6 %), 70 (97.2 %), and 50 (69.1 %) achieved CR, and 48 (66.7 %), 61 (84.7 %) and 49 (68.1 %) achieved CP during in the overall, acute, and delayed phases of cisplatin administration, respectively. Approximately half of the patients had some degree of anorexia. FLIE results indicated that 78.6 % of patients maintained their quality of life. Palonosetron was not superior to granisetron in combination antiemetic therapy. Conclusions Three-drug combination antiemetic therapy with palonosetron, aprepitant, and dexamethasone was tolerable in gastric cancer patients undergoing treatment with S-1 plus cisplatin. The predominance of palonosetron to granisetron was not demonstrated in this study. Abstract Purpose The purpose of our study was to evaluate the efficacy of a new combination antiemetic therapy consisting of palonosetron, aprepitant, and dexamethasone in gastric cancer patients undergoing chemotherapy with S-1 plus cisplatin. Methods This prospective, multi-institutional observational study assessed patient-reported nausea, vomiting, use of rescue therapy, change of dietary intake, and Functional Living Index-Emesis (FLIE) questionnaire results. The percentages of patients showing complete response (CR; no emesis and non-use of any rescue antiemetics) and complete protection (CP; no significant nausea and nonuse of any rescue antiemetics), change of dietary intake, and impact of chemotherapy-induced nausea and vomiting on daily life during the overall (0-120 h after cisplatin administration), acute (0-24 h), and delayed (24-120 h) phases were examined. These findings were compared with Digestive Disease Support Organization (DDSO) 35-1 Yonemarumachi

Correction: Regeneration of esophagus using a scaffold-free biomimetic structure created with bio-three-dimensional printing.

[This corrects the article DOI: 10.1371/journal.pone.0211339.]

Regeneration of esophagus using a scaffold-free biomimetic structure created with bio-three-dimensional printing

Various strategies have been attempted to replace esophageal defects with natural or artificial substitutes using tissue engineering. However, these methods have not yet reached clinical application because of the high risks related to their immunogenicity or insufficient biocompatibility. In this study, we developed a scaffold-free structure with a mixture of cell types using bio-three-dimensional (3D) printing technology and assessed its characteristics in vitro and in vivo after transplantation into rats. Normal human dermal fibroblasts, human esophageal smooth muscle cells, human bone marrow-derived mesenchymal stem cells, and human umbilical vein endothelial cells were purchased and used as a cell source. After the preparation of multicellular spheroids, esophageal-like tube structures were prepared by bio-3D printing. The structures were matured in a bioreactor and transplanted into 10-12- week-old F344 male rats as esophageal grafts under general anesthesia. Mechanical and histochemical assessment of the structures were performed. Among 4 types of structures evaluated, those with the larger proportion of mesenchymal stem cells tended to show greater strength and expansion on mechanical testing and highly expressed α-smooth muscle actin and vascular endothelial growth factor on immunohistochemistry. Therefore, the structure with the larger proportion of mesenchymal stem cells was selected for transplantation. The scaffold-free structures had sufficient strength for transplantation between the esophagus and stomach using silicon stents.The structures were maintained in vivo for 30 days after transplantation. Smooth muscle cells were maintained, and flat epithelium extended and covered the inner surface of the lumen. Food had also passed through the structure. These results suggested that the esophagus-like scaffold-free tubular structures created using bio-3D printing could hold promise as a substitute for the repair of esophageal defects