Background Given the high morbidity and mortality rates for surgery and the diminishment of quality of life caused by operative resection of the gastric cardia, a minor invasive treatment without ...loss of curability is desirable for submucosal tumors (SMTs) of the esophagogastric junction (EGJ). Endoscopic submucosal dissection (ESD) has been used successfully for the removal of esophageal or gastric SMTs; however, the EGJ has been regarded as a difficult location for ESD because of its narrow lumen and sharp angle. Objective To evaluate the clinical impact of ESD for SMTs of the EGJ arising from the muscularis propria layer. Design Single-center, prospective study. Setting Academic medical center. Patients 143 patients with 143 SMTs of the EGJ originating from the muscularis propria layer. Interventions ESD. Main Outcome Measurements Complications, en bloc resection rate, local recurrence, and distant metastases. Results The average maximum diameter of the lesions was 17.6 mm (range 5 - 50 mm). The en bloc resection rate was 94.4% (135/143). All en bloc resection lesions showed both lateral and deep tumor-free margins, including 20 GI stromal tumors. Perforations occurred in 6 patients (4.2%, 6/143), and metal clips were used to occlude the defect. Four pneumoperitoneum and 2 pneumothorax caused by perforations were resolved with nonsurgical treatment. Local recurrence and distant metastasis have not occurred during a 2-year follow-up. Limitations Single-center, short follow-up. Conclusions ESD appears to be a safe, feasible, and effective procedure for providing accurate histopathologic evaluations, as well as curative treatments for SMTs of the EGJ originating from the muscularis propria layer.
Background Peroral endoscopic myotomy (POEM) has been developed to provide a less-invasive myotomy for achalasia in adults but seldom has been used in pediatric patients. Objective To evaluate the ...feasibility, safety, and efficacy of POEM for pediatric patients with achalasia. Design Single-center, prospective study. Setting Academic medical center. Patients A total of 27 pediatric patients (mean age 13.8 years, range 6-17 years) with achalasia. Interventions POEM. Main Outcome Measurements The primary outcome was symptom relief during follow-up, defined as an Eckardt score of ≤3. Secondary outcomes were procedure-related adverse events, clinical reflux adverse events, and lower esophageal sphincter (LES) pressure on manometry before and after POEM. Results A total of 26 cases (96.3%) underwent successful POEM. A submucosal tunnelling attempt failed in 1 case because of serious inflammation and adhesion. No serious adverse events related to POEM were encountered. During a mean follow-up period of 24.6 months (range 15-38 months), treatment success was achieved in all patients (mean score before vs after treatment 8.3 vs 0.7; P < .001). Mean LES pressure also decreased from a mean of 31.6 mm Hg to 12.9 mm Hg after POEM ( P < .001). Five patients developed clinical reflux adverse events (19.2%). Limitations Single center and lack of some objective evaluations. Conclusion This relatively long-term follow-up study adds to the evidence that POEM seems to be a promising new treatment for pediatric patients with achalasia, resulting in long-term symptom relief in all cases and without serious adverse events.
Background A circular muscle myotomy preserving the longitudinal outer esophageal muscular layer is often recommended during peroral endoscopic myotomy (POEM) for achalasia. However, because the ...longitudinal muscle fibers of the esophagus are extremely thin and fragile, and completeness of myotomy is the basis for the excellent results of conventional surgical myotomy, this modification needs to be further debated. Here, we retrospectively analyzed our prospectively maintained POEM database to compare the outcomes of endoscopic full-thickness and circular muscle myotomy. Study Design According to the myotomy depth, 103 patients with full-thickness myotomy were assigned to group A, while 131 patients with circular muscle myotomy were assigned to group B. Symptom relief, procedure-related parameters and adverse events, manometry outcomes, and reflux complications were compared between groups. Results The mean operation times were significantly shorter in group A compared with group B (p = 0.02). There was no increase in any procedure-related adverse event after full-thickness myotomy (all p < 0.05). During follow-up, treatment success (Eckardt score ≤ 3) persisted for 96.0% (95 of 99) of patients in group A and for 95.0% (115 of 121) of patients in group B (p = 0.75). There were no statistically significant differences in pre- and post-treatment D-value of symptom scores and lower esophageal sphincter pressures between groups (both p > 0.05). The overall clinical reflux complication rates were also similar (21.2% vs 16.5%, p = 0.38). Conclusions Short-term symptom relief and manometry outcomes of each method were comparable. Full-thickness myotomy significantly reduced the procedure time but did not increase the procedure-related adverse events or clinical reflux complications.
Summary Our aim was to investigate the expression of micro-RNA-200b (miR-200b) and cAMP-responsive element-binding protein 1 (CREB-1) in astrocytoma and its efficacy for predicting outcome. Both ...miR-200b and CREB-1 messenger RNA expression was measured in 122 astrocytomas and 30 nonneoplastic brain specimens by quantitative real-time polymerase chain reaction. Expression of miR-200b was significantly lower in astrocytoma than in nonneoplastic brain ( P < .001), whereas CREB-1 messenger RNA expression was significantly elevated in the tumors ( P < .001). Both miR-200b down-regulation and CREB-1 up-regulation were significantly associated with advanced pathologic grade ( P = .002 and P = .006, respectively). Low miR-200b expression correlated negatively with Karnofsky performance score ( P = .03), and high CREB-1 expression correlated positively with mean tumor diameter ( P = .03). By Kaplan-Meier analysis, low miR-200b, high CREB-1, and coexistence of abnormal miR-200b and CREB-1 expression (low miR-200b/high CREB-1) were predictive of shorter progression-free survival and overall survival in both grade III and grade IV astrocytoma. By multivariate analysis, only low miR-200b/high CREB-1 expression was an independent prognostic factor for poor prognosis in astrocytoma of advanced grade. Both miR-200b and CREB-1 may play important cooperative roles in the progression of human astrocytoma. The efficacy of miR-200b and CREB-1 together as a predictor of prognosis in astrocytoma patients is shown for the first time.
Background
Colorectal cancer (CRC) represents the third most common malignant tumor in the worldwide. Radiotherapy is the common therapeutic treatment for CRC, but radiation resistance is often ...encountered. ChIP-seq of Histone H3K27 acetylation (H3K27ac) has revealed enhancers that play an important role in CRC. This study examined the relationship between an active CRC enhancer and claudin-1 (CLDN1), and its effect on CRC radiation resistance.
Methods
The target CRC genes of active enhancers were obtained from public H3K27ac ChIP-seq, and the genes highly expressed in radio-resistant CRC were screened and intersected with enhancer-driven genes. The clinical roles of CLDN1 in radiation resistance were examined using the t-test, standard mean deviation (SMD), summary receiver operating characteristic curve and Kaplan-Meier curves. The co-expressed genes of CLDN1 were calculated using Pearson Correlation analysis, and Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes and Gene Set Variation Analysis (GSVA) analyses were used to examine the molecular mechanisms of CLDN1.
Results
Total 13 703 CRC genes were regulated by enhancers using 58 H3K27ac ChIP-seq. Claudin-1 (CLDN1) was enhancer-driven and notably up-regulated in CRC tissues compared to non-CRC controls, with a SMD of 3.45 (95 CI % = .56-4.35). CLDN1 expression was increased in radiation-resistant CRC with a SMD of .42 (95% CI = .16-.68) and an area under the curve of .74 (95% CI = .70-.77). The cell cycle and immune macrophage levels were the most significant pathways associated with CLDN1.
Conclusion
CLDN1 as an enhancer-regulated gene that can boost radiation resistance in patients with CRC.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Background The technique of endoscopic submucosal dissection (ESD), which was developed for en bloc resection of large lesions in the stomach, has been widely accepted for the treatment of early ...gastric cancer. It is being used for muscularis propria tumors of the digestive tract and has produced positive therapeutic effects. Objective To study the feasibility of ESD for the removal of esophageal muscularis propria tumors and to evaluate the efficacy and safety of ESD for this treatment. Design Single-center, retrospective study. Setting University hospital. Patients Thirty esophageal muscularis propria tumors from 28 patients were treated with ESD between December 2008 and December 2010. We defined esophageal muscularis propria tumors as esophageal submucosal tumors originating from the muscularis propria layer. Intervention ESD. Main Outcome Measurements Tumor characteristics, complications, en bloc resection rate, and local recurrence rate were evaluated. Results Among the 28 patients, 11 were women (39.3%). The median age was 49.32 years (range 22-62 years). Mean (±SD) tumor size was 1.25 ± 0.70 cm (range 0.5-3.0 cm). Except for 2 failed cases (one changed to surgery and the other changed to nylon ligation), 26 cases with 28 tumors (2 cases had 2 tumors) originating from the muscularis propria of the esophagus were successfully resected by ESD. The en bloc resection rate was 93.3% (28/30). The median ESD procedure time was 73.5 minutes (range 30-120 minutes). Perforation occurred in 2 cases during dissection of the lesion, which was closed with metal endoclips. Pneumothorax occurred after the treatment in both cases. Closed thoracic drainages were initiated, and the patients recovered quickly without surgery. Pathological examination confirmed 27 leiomyomas and 1 GI stromal tumor. The curative resection rate was 100% (28/28). There was no recurrence during a 3 to 27–month follow-up period. Limitations The limitation of the study was its retrospective design. Conclusion ESD offers the promise of localized treatment of esophageal muscularis propria tumors with relatively few complications and low mortality. It makes the resection of whole lesions possible and provides precise histologic information.
Background Peroral endoscopic myotomy (POEM) is a promising new endoscopic method for the treatment of achalasia. Objective The aim of this study was to analyze the value of routine postoperative CT ...of the chest to detect POEM-associated adverse events. Design Single-center, retrospective study. Setting Tertiary care center. Patients and Interventions Between August 2010 and July 2012, 428 patients underwent POEM. Three hundred postprocedure CT POEM patients were retrospectively analyzed and findings correlated with clinical outcome and management. Main Outcome Measurements The frequency of postoperative pathological CT scan findings after POEM and the rate of interventions required for adverse event management. Results The main CT findings could be divided into frequent and reversible sequelae of POEM, pneumomediastinum (48%), pneumoperitoneum (37%), and subcutaneous emphysema (28%), and into potential adverse events such as pneumothorax (17%), pleural effusion (66%), pneumonitis (52%), and focal atelectasis (21%). Only 17 of 50 patients with pneumothorax (5.6% of all patients) and 2 of 200 patients with pleural effusion (0.7% of all patients) required interventional treatment based on clinical symptoms. In 1 patient, a hematoma was observed on a CT scan before any clinical manifestation occurred. Increasing age and the use of air instead of CO2 were associated with an increased rate of pneumothorax ( P = .031; 95% confidence interval, 1.002-1.049 and P < .001; 95% confidence interval, 0.012-0.157, respectively). Limitations Single-center, retrospective study. Conclusions Routine chest CT scan for achalasia patients undergoing POEM is probably not warranted because of the high rate of minor and clinically irrelevant findings. The use of CO2 is obligatory to reduce related adverse events.
Background Prospective evidence on the association between secondhand smoke (SHS) and COPD and ischemic stroke is scarce. Methods We prospectively examined the relationship between SHS and major ...tobacco-related deaths, particularly COPD and stroke, in 910 Chinese (439 men, 471 women) who never smoked from a 17-year follow-up study in Xi'an, China. SHS exposure was defined as exposure to another person's tobacco smoke at home or in the workplace. Results At baseline among the 910 subjects, 44.2% were exposed to SHS at home, 52.9% in the workplace, and 67.1% at home, work, or both. From March 1, 1994, to July 1, 2011, 249 (150 men, 99 women) died within 14,016 person-years. Those who were exposed to SHS had increased mortality due to coronary heart disease (adjusted relative risk RR, 2.15; 95% CI, 1.00-4.61), ischemic stroke (RR, 2.88; 95% CI, 1.10-7.55), lung cancer (RR, 2.00; 95% CI, 0.62-6.40), COPD (RR, 2.30; 95% CI, 1.06-5.00), and all causes (RR, 1.72; 95% CI, 1.29-2.20), with significant dose-response relationships between cumulative SHS exposure at home and work and the increased risk of cause-specific and total mortality ( P for linear trend ranged from .045 to <.001). Conclusions This study shows dose-response relationships between SHS and major tobacco-related mortality and provides new evidence to support causation for COPD and ischemic stroke.
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