Objective To determine dermoscopic findings of alopecia areata (AA) from a large‐scale study that can be used as clinical indicators of disease.
Methods Dermoscopic examination of areas of hair ...loss on the scalp of 300 Asian patients with AA was performed using a DermLite® II pro, which can block light reflection from the skin surface without immersion gels. Using the Spearman rank‐order correlation coefficient by rank test, correlations between the incidence of each dermoscopic finding and the severity of disease and disease activity were examined. The sensitivity and specificity of the findings as diagnostic clues for AA were evaluated.
Results Characteristic dermoscopic findings of AA included black dots, tapering hairs, broken hairs, yellow dots, and clustered short vellus hairs (shorter than 10 mm) in the areas of hair loss. Black dots, yellow dots, and short vellus hairs correlated with the severity of disease, and black dots, tapering hairs, broken hairs, and short vellus hairs correlated with disease activity. For diagnosis, yellow dots and short vellus hairs were the most sensitive markers, and black dots, tapering hairs, and broken hairs were the most specific markers.
Conclusion Dermoscopic characteristics, such as black dots, tapering hairs, broken hairs, yellow dots, and clustered short vellus hairs, are useful clinical indicators for AA.
The depth of invasion of the bowel wall influences the treatment of colorectal laterally spreading tumors (LSTs). The aim of this study was to evaluate the risk factors and patterns of submucosal ...invasion in a large series of LSTs that were removed en bloc.
Prospectively collected endoscopic and pathological data on a total of 822 LSTs, ≥ 10 mm in size and removed en block by endoscopic submucosal dissection (n = 670) or surgery (n = 152), were retrospectively analyzed.
In 414 LSTs of the granular type, submucosal invasion was detected in 80 cases (19 %; 95 % confidence interval CI 16 - 23) and was deep (≥ 1000 μm) in 79 % of cases. The invasion site was under a large (≥ 10 mm) nodule (56 %), depression (28 %), or was multifocal (16 %). Risk factors for deep submucosal invasion on multivariate analysis were the presence of a large nodule (odds ratio OR 12, 95 %CI 2 - 59), depression (OR 59, 95 %CI 9 - 387), and invasive pit pattern (OR 33, 95 %CI 12 - 88). The sensitivity and specificity of invasive pit pattern for detection of deep submucosal invasion were 52 % (95 %CI 40 % - 64 %) and 98 % (95 %CI 96 % - 99 %), respectively.In 408 LSTs of the nongranular type, submucosal invasion was detected in 159 cases (39 %; 95 %CI 34 - 44) and was deep in 54 % of cases. The invasion site was under a submucosal mass-like elevation (10 %), depression (45 %), or was multifocal (45 %). Risk factors for deep submucosal invasion were the presence of a submucosal mass-like elevation (OR 8, 95 %CI 1 - 61), depression (OR 28, 95 %CI 8 - 97), and invasive pit pattern (OR 79, 95 %CI 25 - 256).
Because of a substantial risk of submucosal invasion and multifocal invasion, granular type LSTs with a large nodule or depression and nongranular type LSTs should be endoscopically removed en bloc.
Background
Helicobacter pylori
(
HP
) infection potently induces aberrant DNA methylation in gastric mucosae, and its accumulation is associated with gastric cancer risk. Cross-sectional analysis of ...methylation levels (fraction of methylated DNA molecules) and temporal analysis of methylation incidence suggested that methylation levels decrease after
HP
infection discontinues. We aimed to demonstrate the decrease in methylation levels.
Methods
Thirty-five patients with
HP
infection who had undergone curative endoscopic resection and 11 healthy volunteers were recruited. Methylation levels were quantified by real-time methylation-specific PCR. Histology was evaluated according to the updated Sydney System.
Results
In the 20 patients with successful eradication, the
FLNc
methylation level, along with infiltration of inflammatory cells, decreased from 0.6 to 0.4% at 6 weeks (
P
= 0.049) and remained low at 1 year. The
THBD
methylation level (30.1%) remained high at 6 weeks, but decreased to 19.0% at 1 year (
P
= 0.0032). Nine healthy volunteers with successful eradication tended to show a decrease of both
FLNc
and
THBD
at 6 weeks. However, the methylation levels after the decrease were still higher than those of healthy individuals without
HP
infection. In the 15 patients with persistent infection, the methylation levels remained the same. Before eradication, the
THBD
methylation level correlated with the degree of inflammatory cell infiltration (
P
<
0.05).
Conclusions
Methylation levels in gastric mucosae decreased to certain levels after
HP
eradication in profiles unique to individual markers. Involvement of chronic inflammation in methylation induction was suggested.
Genetic and epigenetic alterations are both involved in carcinogenesis, and their low-level accumulation in normal tissues constitutes cancer risk. However, their relative importance has never been ...examined, as measurement of low-level mutations has been difficult. Here, we measured low-level accumulations of genetic and epigenetic alterations in normal tissues with low, intermediate, and high cancer risk and analyzed their relative effects on cancer risk in the esophagus and stomach. Accumulation of genetic alterations, estimated as a frequency of rare base substitution mutations, significantly increased according to cancer risk in esophageal mucosae, but not in gastric mucosae. The mutation patterns reflected the exposure to lifestyle risk factors. In contrast, the accumulation of epigenetic alterations, measured as DNA methylation levels of marker genes, significantly increased according to cancer risk in both tissues. Patients with cancer (high-risk individuals) were precisely discriminated from healthy individuals with exposure to risk factors (intermediate-risk individuals) by a combination of alterations in the esophagus (odds ratio, 18.2; 95% confidence interval, 3.69–89.9) and by only epigenetic alterations in the stomach (odds ratio, 7.67; 95% confidence interval, 2.52–23.3). The relative importance of epigenetic alterations upon genetic alterations was 1.04 in the esophagus and 2.31 in the stomach. The differential impacts among tissues will be critically important for effective cancer prevention and precision cancer risk diagnosis.
Aberrant methylation of CpG islands in promoter regions can permanently inactivate tumor-suppressor genes, as mutations and chromosomal abnormalities do. In gastric cancers, CDKN2A, CDH1, and MLH1 ...are inactivated more frequently by aberrant methylation than by mutations, and novel tumor-suppressor genes inactivated by promoter methylation are being identified. We recently found that Helicobacter pylori (HP), a potent gastric carcinogen, induces aberrant methylation in gastric mucosae. When a panel of CpG islands was examined, some CpG islands were consistently methylated in gastric mucosae of individuals with HP infection, while others were resistant. The amount of methylated DNA molecules in the gastric mucosae (methylation level) fluctuated while active HP infection was present, but decreased after it was no longer present. Among individuals without active HP infection, methylation levels in the gastric mucosae were higher in individuals with gastric cancers than in those without. DNA methylation is emerging as a promising marker for past exposure to carcinogens and future risk of cancers.
microRNAs (miRNAs) are small noncoding RNAs that negatively regulate gene expression. They are found within cells and in body fluids. Extracellular miRNAs have been shown to associate with the ...surrounding tissues. Therefore, we predicted that miRNAs in tears may contribute to regulate corneal epithelial cell function. However, information on the miRNA expression profile of tears is limited and the specific functions of tear miRNAs for corneal epithelial cells are still unknown. To study the role of tear miRNAs, we determined which miRNAs are highly expressed in tears and examined the involvement of miRNAs in corneal epithelial cell viability.
miRNAs extracted from monkey tears and sera were subjected to microarray analysis. miRNAs of which expression levels were higher in tears than in sera were selected, and their expression levels were quantified by quantitative polymerase chain reaction (qPCR). To examine miRNA function, mimics and inhibitors of miRNAs were transfected into human corneal epithelial (HCE-T) cells and incubated for 24 or 48 h. After transfection of miRNA mimics and inhibitors, the viability of HCE-T cells was measured using the water soluble tetrazolium salt (WST) assay, and microarray analysis and qPCR were performed using total RNA extracted from HCE-T cells. siRNAs of the candidate targets for miR-203 were transfected into HCE-T cells and the WST assay was performed. To determine a direct target gene for miR-203, a dual luciferase reporter assay was performed in HCE-T cells using a luciferase reporter plasmid containing 3'-UTR of human IGFBP5.
Microarray and qPCR analyses showed that miR-184 and miR-203 were expressed significantly more highly in tears than in sera (165,542.8- and 567.8-fold, respectively, p < 0.05). Of these two miRNAs, transfection of a miR-203 mimic significantly reduced the viability of HCE-T cells (p < 0.05), while a miR-203 inhibitor significantly increased this viability (p < 0.05). miR-203 mimic downregulated insulin-like growth factor-binding protein 5 (IGFBP5) and nuclear casein kinase and cyclin-dependent kinase substrate 1 (NUCKS1), while miR-203 inhibitor upregulated these two genes. Transfection of IGFBP5-siRNA decreased the viability of HCE-T cells. miR-203 mimic significantly diminished the luciferase reporter activity.
In this study, we identified miRNAs that are highly expressed in tears, and the inhibition of miR-203 increases the viability of corneal epithelial cells. Our results suggest that miR-203 contributes to regulating the homeostasis of corneal epithelial cells.
Endoscopic submucosal dissection (ESD) is known as a curative treatment for colorectal superficial neoplasms. There is however a need for more long-term clinical data to establish the full advantages ...of colorectal ESD regarding very low recurrence rates. The aim of this retrospective study was to determine long-term clinical outcomes of colorectal ESD.
A total of 423 lesions treated by ESD for colorectal adenoma/dysplasia or adenocarcinoma between 1998 and 2008 at a single high volume referral center were included. We conducted a retrospective survey on patients with follow-up and obtained complete 1-, 3-, and 5-year outcome data for 358 (85 %), 292 (69 %), and 209 (49 %) lesions, respectively. Curative resection was defined when the pathological specimen had carcinoma-free resection margins, irrespective of piecemeal or en bloc resection, without submucosal deep invasion (≥ 1000 µm), lymphovascular involvement, or a poorly differentiated adenocarcinoma component.
After a median 4.9 years of follow-up, the 3-year overall cumulative endoscopic recurrence rate and cancerous recurrence rate were 2.9 % (95 % confidence interval 95 %CI 1.2 - 4.7) and 1.1 % (0 - 2.1), respectively. The 5-year overall cumulative endoscopic recurrence and cancerous recurrence rates were 3.8 % (1.7 - 5.9) and 1.6 % (0.1 - 3.0), respectively. In 361 lesions eligible for endoscopic follow-up, the 3-year endoscopic recurrence and cancerous recurrence rates were 2.4 % (0.8 - 4.1) and 0.4 % (0 - 1.4), respectively. Multivariate analysis revealed that piecemeal resection and submucosal deep tumor invasion were associated with recurrence.
The current study demonstrated favorable long-term clinical outcomes of colorectal ESD when en bloc curative resection is achieved.
This study aimed to clarify whether short-term neurofeedback training during the acute stroke phase led to prefrontal activity self-regulation, providing positive efficacy to working memory. A total ...of 30 patients with acute stroke performed functional near-infrared spectroscopy-based neurofeedback training for a day to increase their prefrontal activity. A randomized, Sham-controlled, double-blind study protocol was used comparing working memory ability before and after neurofeedback training. Working memory was evaluated using a target-searching task requiring spatial information retention. A decline in spatial working memory performance post-intervention was prevented in patients who displayed a higher task-related right prefrontal activity during neurofeedback training compared with the baseline. Neurofeedback training efficacy was not associated with the patient's clinical background such as Fugl-Meyer Assessment score and time since stroke. These findings demonstrated that even short-term neurofeedback training can strengthen prefrontal activity and help maintain cognitive ability in acute stroke patients, at least immediately after training. However, further studies investigating the influence of individual patient clinical background, especially cognitive impairment, on neurofeedback training is needed. Current findings provide an encouraging option for clinicians to design neurorehabilitation programs, including neurofeedback protocols, for acute stroke patients.
As more early gastric cancer (EGC) patients are being treated with endoscopic submucosal dissection (ESD), it is important to understand the outcomes of patients who develop metachronous gastric ...cancer (MGC). The aim of this study was to evaluate the long-term surveillance and treatment outcomes of MGC after curative gastric ESD.
The study included 1526 consecutive patients who underwent curative ESD resection of EGC. They were generally followed by annual or biannual esophagogastroduodenoscopy. The risk factors and treatment outcomes for MGC were assessed along with the 5-year, 7-year, and 10-year cumulative incidence functions of MGC and disease-specific survival (DSS).
During a median follow-up period of 82.2 months, 238 patients developed MGC post-ESD resection of EGC. The 5-year, 7-year, and 10-year cumulative incidence functions of MGC were 9.5%, 13.1% and 22.7%, respectively. Male sex and multiple initial EGCs were independent risk factors for MGC in the Cox proportional hazard model. Of the 238 patients with MGC, 215 were treated with endoscopic resection, of which 183 achieved curative resection, although one patient later died of his initial EGC. A further 14 patients were treated surgically, three had metastatic disease and received palliative chemotherapy, and the remaining six were observed without any intervention. A total of seven patients died of MGC, five at least 5 years after their index ESD. The 5-year, 7-year, and 10-year DSSs were 99.2%, 98.6%, and 92.5%, respectively.
The incidence of MGC increases with time after curative gastric ESD, therefore surveillance endoscopy should be continued indefinitely.
Because light‐emitting diodes (LEDs) are low‐coherent, quasimonochromatic, and nonthermal, they are an alternative for low level laser therapy, and have photobiostimulative effects on tissue repair. ...However, the molecular mechanism(s) are unclear, and potential effects of blue and/or green LEDs on wound healing are still unknown. Here, we investigated the effects of red (638 nm), blue (456 nm), and green (518 nm) LEDs on wound healing. In an in vivo study, wound sizes in the skin of ob/ob mice were significantly decreased on day 7 following exposure to green LEDs, and complete reepithelialization was accelerated by red and green LEDs compared with the control mice. To better understand the molecular mechanism(s) involved, we investigated the effects of LEDs on human fibroblasts in vitro by measuring mRNA and protein levels of cytokines secreted by fibroblasts during the process of wound healing and on the migration of HaCat keratinocytes. The results suggest that some cytokines are significantly increased by exposure to LEDs, especially leptin, IL‐8, and VEGF, but only by green LEDs. The migration of HaCat keratinocytes was significantly promoted by red or green LEDs. In conclusion, we demonstrate that green LEDs promote wound healing by inducing migratory and proliferative mediators, which suggests that not only red LEDs but also green LEDs can be a new powerful therapeutic strategy for wound healing.
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