SEDATION WITH DEXMEDETOMIDINE HYDROCHLORIDE DURING ENDOSCOPIC SUBMUCOSAL DISSECTION OF GASTRIC CANCER

Aim: Although the treatment of early gastric cancer with endoscopic submucosal dissection (ESD) has been widely carried out, a standardized method of sedation for ESD has not been established. The purpose of the present study was to evaluate the efficacy and safety of sedation with dexmedetomidine (DEX). Methods: We conducted a randomized study involving 90 patients with gastric tumors who were intended to be treated with ESD. The patients were sedated either with DEX (i.v. infusion of 3.0 µg/kg per h over 5 min followed by continuous infusion at 0.4 µg/kg per h [n = 30]), propofol (PF [n = 30]), or midazolam (MDZ [n = 30]). In all groups, 1 mg MDZ was added i.v. as needed. Results: En bloc resection of the gastric tumor was achieved in 88 (98%) patients. None of the DEX‐sedated patients showed a significant reduction of the oxygen saturation level. The percentage of patients who showed body movement in the DEX group was significantly lower than those in the PF and MDZ groups, and the mean dose of additional MDZ in the DEX group was significantly smaller than that in the MDZ group. The rate of effective sedation was significantly higher in the DEX group compared with the MDZ or PF group. The mean length of ESD in the DEX group was 65 min, which was significantly shorter than in the other two groups. No DEX‐sedated patient developed major surgical complications. Conclusions: Sedation with DEX is effective and safe for patients with gastric tumors who are undergoing ESD.     

Nicotine does not affect stem cell properties requisite for suicide gene therapy against glioma

ABSTRACT

Objective: 

Glioblastoma is one of the most lethal tumors in adult central nervous system with a median survival of a year and half and effective therapeutic strategy is urgently needed. For that reason, stem cell-based suicide gene therapies have attracted much interest because of potent tumor tropism of stem cells and bystander effect. In this current clinical situation, stem cells are promising delivery tool of suicide genes for glioma therapy. Since habitual cigarette smoking still prevails worldwide, we investigated the effect of nicotine on stem cell tropism toward glioma and gap junctional intercellular communication (GJIC) function between glioma and stem cells, both of which are important for suicide gene therapies. Methods: Mouse induced pluripotent stem cell-derived neural stem cells (iPS-NSCs) and human dental pulp mesenchymal stem cells (DPSCs) were used. The effect of nicotine on tumor tropism to glioma-conditioned medium (CM) at a non-cytotoxic concentration was assessed with Matrigel invasion assay. Nicotine effect on GJIC was assessed with the scrape loading/dye transfer (SL/DT) assay for co-culture of glioma and stem cells and the parachute assay among glioma cells using high-content analysis. Results: Tumor tropism of iPS-NSCs toward GL261-CM and DPSCs toward U251-CM was not affected by nicotine (0.1 and 1 µM). Nicotine at the concentrations equivalent to habitual smoking (1 µM) did not affect GJIC of iPS-NSC/GL261 and DPSC/U251 and GJIC among each glioma cells. Conclusions: The study demonstrated that non-cytotoxic concentrations of nicotine did not significantly change the stem cell properties requisite for stem cell-based suicide gene therapy.     

Treatment outcome of laparoscopic surgery after self-expandable metallic stent insertion for obstructive colorectal cancer

International Journal of Clinical Oncology - We assessed the technical and oncological safety of self-expandable metallic stent (SEMS) insertion followed by laparoscopic colorectal surgery as a...     

Fusobacterium nucleatum confers chemoresistance by modulating autophagy in oesophageal squamous cell carcinoma

Background Fusobacterium nucleatum (F. nucleatum) is a gut microbe implicated in gastrointestinal tumorigenesis. Predicting the chemotherapeutic response is critical to developing personalised therapeutic strategies for oesophageal cancer patients. The present study investigated the relationship between F. nucleatum and chemotherapeutic resistance in oesophageal squamous cell carcinoma (ESCC).Methods We examined the relationship between F. nucleatum and chemotherapy response in 120 ESCC resected specimens and 30 pre-treatment biopsy specimens. In vitro studies using ESCC cell lines and co-culture assays further uncovered the mechanism underlying chemotherapeutic resistance.Results ESCC patients with F. nucleatum infection displayed lesser chemotherapeutic response. The infiltration and subsistence of F. nucleatum in the ESCC cells were observed by transmission electron microscopy and laser scanning confocal microscopy. We also observed that F. nucleatum modulates the endogenous LC3 and ATG7 expression, as well as autophagosome formation to induce chemoresistance against 5-FU, CDDP, and Docetaxel. ATG7 knockdown resulted in reversal of F. nucleatum-induced chemoresistance. In addition, immunohistochemical studies confirmed the correlation between F. nucleatum infection and ATG7 expression in 284 ESCC specimens.Conclusions F. nucleatum confers chemoresistance to ESCC cells by modulating autophagy. These findings suggest that targeting F. nucleatum, during chemotherapy, could result in variable therapeutic outcomes for ESCC patients.Subject terms: Tumour biomarkers, Oesophageal cancer     

Square-stepping exercise and fall risk factors in older adults: a single-blind, randomized controlled trial

BACKGROUND: Decreased fitness of the lower extremities is a potentially modifiable fall risk factor. This study aimed to compare two exercise programs--square-stepping exercise (SSE), which is a low-cost indoor program, and walking--for improving the fitness of the lower extremities. METHODS: We randomly allocated 68 community-dwelling older adults (age 65-74 years) to either the SSE or walking group (W group). During the 12-week regimen, the SSE group participated in 70-minute exercise sessions conducted twice a week at a local health center, and the W group participated in outdoor supervised walking sessions conducted weekly. The W group was instructed to increase the number of daily steps. Prior to and after the program, we obtained information on 11 physical performance tests for known fall risk factors and 3 self-reported scales. The fall incidence was followed-up for 8 months. RESULTS: At 12 weeks postregimen, significant differences were observed between the two exercise groups with respect to leg power (1 item), balance (2 items), agility (2 items), reaction time (2 items), and a self-reported scale (1 item); the SSE group demonstrated a marked improvement in the above-mentioned items with Group x Time interactions. Significant time effects were observed in the tests involving chair stands, functional reach, and standing up from a lying-down position without Group x Time interactions. During the follow-up period, the fall rates per person-year in the SSE and W groups were 23.4% and 33.3%, respectively (p =.31). CONCLUSION: Although further studies are required, SSE is apparently more effective than walking in reducing fall risk factors, and it appears that it may be recommended as a health promotion exercise in older adults.