It is established that deep brain stimulation of the subthalamic nucleus improves motor function in advanced Parkinson’s disease, but its effects on autonomic function remain to be elucidated. The present study was undertaken to investigate the effects of subthalamic deep brain stimulation on gastric emptying. A total of 16 patients with Parkinson’s disease who underwent bilateral subthalamic deep brain stimulation were enrolled. Gastric emptying was expressed as the peak time of 13CO2 excretion (Tmax) in the 13C-acetate breath test and was assessed in patients with and without administration of 100–150 mg levodopa/decarboxylase inhibitor before surgery, and with and without subthalamic deep brain stimulation at 3 months post-surgery. The pattern of 13CO2 excretion curve was analysed. To evaluate potential factors related to the effect of subthalamic deep brain stimulation on gastric emptying, we also examined the association between gastric emptying, clinical characteristics, the equivalent dose of levodopa and serum ghrelin levels. The peak time of 13CO2 excretion (Tmax) values for gastric emptying in patients without and with levodopa/decarboxylase inhibitor treatment were 45.6 ± 22.7 min and 42.5 ± 13.6 min, respectively (P = not significant), thus demonstrating levodopa resistance. The peak time of 13CO2 excretion (Tmax) values without and with subthalamic deep brain stimulation after surgery were 44.0 ± 17.5 min and 30.0 ± 12.5 min (P < 0.001), respectively, which showed that subthalamic deep brain stimulation was effective. Simultaneously, the pattern of the 13CO2 excretion curve was also significantly improved relative to surgery with no stimulation (P = 0.002), although the difference with and without levodopa/decarboxylase inhibitor was not significant. The difference in peak time of 13CO2 excretion (Tmax) values without levodopa/decarboxylase inhibitor before surgery and without levodopa/decarboxylase inhibitor and subthalamic deep brain stimulation after surgery was not significant, although motor dysfunction improved and the levodopa equivalent dose decreased after surgery. There was little association between changes in ghrelin levels (Δghrelin) and changes in Tmax values (ΔTmax) in the subthalamic deep brain stimulation trial after surgery (r = −0.20), and no association between changes in other characteristics and ΔTmax post-surgery in the subthalamic deep brain stimulation trial. These results showed that levodopa/decarboxylase inhibitor did not influence gastric emptying and that subthalamic deep brain stimulation can improve the dysfunction in patients with Parkinson’s disease possibly by altering the neural system that controls gastrointestinal function after subthalamic deep brain stimulation. This is the first report to show the effectiveness of subthalamic deep brain stimulation on gastrointestinal dysfunction as a non-motor symptom in Parkinson’s disease.
Endoscopic submucosal dissection (ESD) has become widely accepted as a standard treatment for gastric epithelial neoplasms. Antithrombotic agents are widely used to prevent thromboembolic disease. However, the feasibility of endoscopic procedures for patients using such agents has been rarely investigated. The aim of this study was to identify risk factors for post-operative bleeding after gastric ESD and to evaluate the relationship between the use of antithrombotic agents and post-operative bleeding. From June 2005 to March 2014, 413 patients with 425 gastric neoplasms were treated by ESD. The demographic and clinical parameters associated with post-operative bleeding were investigated. 83 patients receiving antithrombotic agents were separately assessed using various methods of administration during the ESD procedure. Post-operative bleeding that occurred within 5 days of ESD was defined as early post-operative bleeding, whereas subsequent bleeding was defined as delayed bleeding. The overall post-operative bleeding rate was 4.7%. In patients with continued low-dose aspirin (LDA), heparin replacement (HR), or continued LDA along with HR, post-operative bleeding rates were 9.5%, 23.8%, and 25.0%, respectively. On multivariate analysis, a specimen size of ≥40 mm was a risk factor for early post-operative bleeding [odds ratio (OR) 6.08, 95% CI: 1.74–21.27], and HR and chronic kidney disease (CKD) requiring hemodialysis were risk factors for delayed bleeding (OR 12.23, 95% CI: 2.63–56.77 and OR 28.35, 95% CI: 4.67–172.11, respectively). Continued LDA was not a risk factor for post-operative bleeding. Large specimen size is a risk factor for early post-operative bleeding, and HR and CKD requiring hemodialysis are risk factors for delayed bleeding. Patients with risk factors should be carefully watched, allowing for the timing of post-operative bleeding after ESD.
Functional dyspepsia (FD) is a common disease but there is no established treatment. Rikkunshito is a traditional Japanese medicine that is widely used for treating upper gastrointestinal symptoms and its effect on ghrelin is of great interest. The aim of this study was to investigate the effect of rikkunshito on upper gastrointestinal symptoms and the levels of acylated ghrelin (AG) in patients with FD. This study was a paralleled, randomized controlled trial. Patients were treated with either rikkunshito (group R) or domperidone (group D) for 4 weeks. The overall change in dyspeptic symptoms was evaluated by the GSRS (Gastrointestinal Symptom Rating Scale) questionnaire score. 27 patients were enrolled. There was a significant improvement in dyspeptic symptoms in both groups, based on the GSRS score. AG levels increased significantly in plasma in group R at 2 weeks after treatment (paired t-test, p<0.05). The improvements of reflux (Pearson's correlation test, r=-0.73, p=0.04) and indigestion (r=-0.76, p=0.03) symptoms in group R showed a good correlation with the increase of AG. Rikkunshito improves upper gastrointestinal symptoms in patients with FD, accompanied by an increase in the levels of AG.
This study retrospectively analyzed the clinical outcomes of endoscopic resection of 26 sporadic (i. e., not associated with polyposis syndrome) nonampullary duodenal lesions representing high-grade dysplasia or intramucosal carcinoma (duodenal HGD/IMC) in 23 patients. No severe complications such as perforation were observed, but three cases of delayed bleeding were seen. The use of endoscopic clips significantly decreased the delayed bleeding rate (0 /19, 0 %) compared with cases in which clips were not used (3 /7, 42.9 %; P = 0.013, χ2 test). Eighteen lesions (69.2 %) were removed by en bloc resection. The follow-up period after resection was 25.5 ± 23.3 months. Two lesions (7.7 %) that recurred locally were detected at the first surveillance endoscopy 3 months after resection. These lesions were 22 and 15 mm in size respectively and were resected piecemeal. Endoscopic resection is an effective and safe procedure for treating duodenal HGD/IMC. En bloc resection and prophylactic clip usage are encouraged.
MicroRNAs (miRNA) are non-coding RNAs that negatively control gene expression by cleaving or inhibiting the translation of target gene mRNAs. We used a microarray-based transcriptomic analysis to identify miRNA expression levels that changed in response to epigenetic factors. Specifically, we searched for increased expression of miRNAs prepared from colon cancer cell line DLD-1 after a 96-h treatment with 5 µM of 5-aza-2'-deoxycytidine (DAC). Among those identified, transient transfection of miRNA hsa-miR-373 resulted in cytostasis. In addition, bisulfate sequence analysis of the promoter regions of these miRNAs showed aberrant methylation in the cancer cells. In clinical colon samples, hsa-miR-373 was down-regulated in colon cancers (29/40, 72.5%) relative to control samples, whereas the purported oncogene RAB22A (a target gene of hsa-miR-373) was up-regulated (24/40, 60%). Using methylation-specific PCR, we also observed aberrant methylation of hsa-miR-373 in colon cancers (35/40, 87.5%) relative to controls (8/40, 20%). Based on these results, we conclude that expression of hsa-miR-373 is down-regulated by aberrant methylation in colon cancer and that this miRNA may function by regulating expression of the oncogene RAB22A.