Stereotactic Body Radiation Therapy for Pulmonary Metastasis from Colorectal Adenocarcinoma: Biologically Effective Dose 150 Gy is Preferred for Tumour Control.

AIMS: To compare the local control rate of pulmonary metastatic lesions in colorectal adenocarcinoma treated with stereotactic body radiation therapy (SBRT) using a biologically effective dose with an α/ß ratio of 10 (BED10) of 150 Gy. MATERIALS AND METHODS: We analysed 231 pulmonary metastatic lesions from colorectal adenocarcinoma treated with SBRT in 135 patients. The patients were referred for the control of oligometastatic or oligoprogressive disease in the lungs. A dose of 40-60 Gy in three to eight fractions was delivered. The local control per tumour (LCpT) by BED10 was evaluated. The local control per patient (LCpP), pulmonary progression-free survival (PPFS), any progression-free survival (APFS) and overall survival were also reported as clinical outcomes. RESULTS: A significant difference was observed in the LCpT between the BED10 groups (P < 0.001). The 1-, 2- and 3-year LCpT were 38.9%, 25.9% and 25.9% in BED10 < 100 group; 84.1%, 62.6% and 60.4% in 100 ≤ BED10 < 150 Gy group; and 97.3%, 94.9% and 85.2% in BED10 ≥ 150 Gy group, respectively. BED10 ≥ 150 Gy remained significant in the multivariate analysis of LCpT. The 3-year LCpP, PPFS, APFS and overall survival rates were 62.7%, 26.5%, 24.8% and 67.7%, respectively. Oligoprogression (versus oligometastasis), multiple pulmonary nodules and extrapulmonary metastasis were associated with a poor prognosis. CONCLUSION: A BED10 ≥ 150 Gy may be required to achieve sufficient local control. The indications for SBRT and the extent of metastatic disease should be assessed for proper estimation of the clinical outcomes.

Da Vinci SP robotic approach to colorectal surgery: two specific indications and short-term results.

BACKGROUND: Da Vinci® Single Port (dvSP) was recently developed. Its application in colorectal surgery is under investigation. The aim of this study was to explore the safety and feasibility of dvSP for intersphincteric (dvSP-ISR), right colectomy (dvSP-RC), and transverse colectomy (dvSP-TC). Surgical indication and short-term results were analyzed. METHODS: All consecutive patients from a prospective database of patients who underwent dvSP-ISR, dvSP-RC, and dvSP-TC at Korea University Anam Hospital from November 2020 to December 2021, were analyzed. Perioperative, pathological, and oncological short-term outcomes were analyzed. RESULTS: A total of 7 dvSP-ISR, 5 dvSP-RC, and 1 dvSP-TC were performed. Median age was 56.0 (55.0-61.0) years for the dvSP-ISR and 54.0 (44.7-63.5) years for the dvSP-RC/TC. Median body mass index was 22.8 (17.1-24.8) kg/m2 for the dvSP-ISR and 23.6 (20.8-26.9) kg/m2 for the dvSP-RC/TC. All dvSP-ISR patients received neoadjuvant long-course chemoradiotherapy, including one patient with squamocellular carcinoma who was treated with 5-fluorouracil (5-FU)/mitomycin. All other patients, excluding one dvSP-RC patient with Crohn's disease, had an adenocarcinoma. Median operation time was 280 (240-370) minutes for the dvSP-ISR and 220 (201-270) minutes for the dvSP-RC/TC. Estimated blood loss was insignificant. No intraoperative complications or conversions to multiport/open surgery was reported. Median post-operative stay was 7.0 (6.0-10.0) days for the dvSP-ISR and 5.0 (4.0-6.7) days for the dvSP-RC/TC. Quality of mesorectum was complete for six patients, and nearly complete for one. Median number of retrieved lymph nodes were 21 (17-25) for the dvSP-ISR and 28 (24-49) for the dvSP-RC/TC. Proximal and distal resection margins were tumor free. Four patients experienced post-operative complications not related to the platform which were: ileus, voiding dysfunction, infected pelvic hematoma, and wound infection. Median follow-up was 9 (6-11) months and 11 (7-17) months for the dvSP-ISR and dvSP-RC/TC, respectively. Two patients had systemic recurrence; all others were tumor free. CONCLUSIONS: The dvSP platform is safe and feasible for intersphincteric resection with right lower quadrant access, and right/transverse colectomy with suprapubic access. Further studies are needed to evaluate benefit differences compared to multiport robotic platform.

Increased risk of cardiovascular diseases in patients with chronic rhinosinusitis: a longitudinal follow-up study using a national health screening cohort.

BACKGROUND: Chronic rhinosinusitis (CRS) is one of the most common chronic inflammatory diseases and is characterized by sinonasal inflammation that lasts longer than 12 weeks. Whether the effect of chronic inflammation caused by CRS on cardiovascular diseases (CVDs) is similar to its effect on other inflammatory disorders has not been thoroughly evaluated. We aimed to demonstrate whether CRS patients have a higher prevalence of CVDs, including stroke and ischemic heart disease (IHD). METHODOLOGY: We compared the prevalence of various comorbidities between CRS and control participants through a case-control cohort study from 2002 to 2015 that included 514,866 participants. CRS (n=6,552) and control (n=26,208) participants who were over 40 years old were selected by matching age, sex, income, and area of residence at a 1:4 ratio. RESULTS: A stratified Cox proportional hazards model was utilized to assess the hazard ratio (HR) of CRS for stroke and IHD. The HRs for stroke and IHD were significantly increased in CRS patients compared to controls after adjusting for obesity, alcohol consumption, smoking, systolic and diastolic blood pressure, fasting blood glucose, total cholesterol, hemoglobin, and Charlson Comorbidity Index (CCI) scores. The HR of stroke was significantly higher in the absence of nasal polyps than in the presence of nasal polyps. The HR of IHD was significantly increased in the CRS group regardless of the presence of nasal polyps. CONCLUSIONS: This study showed that CRS participants had a significantly higher prevalence of stroke and IHD.

Risk factors for local recurrence and long term survival after minimally invasive intersphincteric resection for very low rectal cancer: Multivariate analysis in 161 patients.

INTRODUCTION: Intersphincteric resection (ISR) is the ultimate anal-sparing technique as an alternative to abdominoperineal resection in selected patients. Oncological safety is still debated. This study analyses long-term oncological results and evaluates risk factors for local recurrence (LR) and overall survival (OS) after minimally-invasive ISR. MATERIALS AND METHODS: Retrospective single-center data were collected from a prospectively maintained colorectal database. A total of 161 patients underwent ISR between 2008 and 2018. OS and local recurrence-free survival (LRFS) were assessed using Kaplan-Meier analysis (log-rank test). Risk factors for OS and LRFS were assessed with Cox-regression analysis. RESULTS: Median follow-up was 55 months. LR occurred in 18 patients. OS and LRFS rates at 1, 3, and 5 years were 96%, 91%, and 80% and 96%, 89%, and 87%, respectively. Tumor size (p = 0.035) and clinical T-stage (p = 0.029) were risk factors for LRFS on univariate analysis. On multivariate analysis, tumor size (HR 2.546 (95% CI: 0.976-6.637); p = 0.056) and clinical T-stage (HR 3.296 (95% CI: 0.941-11.549); p = 0.062) were not significant. Preoperative CEA (p < 0.001), pathological T-stage (p = 0.033), pathological N-stage (p = 0.016) and adjuvant treatment (p = 0.008) were prognostic factors for OS on univariate analysis. Preoperative CEA (HR 4.453 (95% CI: 2.015-9.838); p < 0.001) was a prognostic factor on multivariate analysis. CONCLUSIONS: This study confirms the oncological safety of minimally-invasive ISR for locally advanced low-lying rectal tumors when performed in experienced centers. Despite not a risk factor for LR, tumor size and, locally advanced T-stage with anterior involvement should be carefully evaluated for optimal surgical strategy. Preoperative CEA is a prognostic factor for OS.

Robotic-assisted resection for beyond TME rectal cancer: a novel classification and analysis from a specialized center.

Locally advanced rectal cancer often requires an extended resection beyond the total mesorectal excision plane (bTME) to obtain clear resection margins. We classified three types of bTME rectal cancer following local disease diffusion: radial (adjacent pelvic organs), lateral (pelvic lateral lymph nodes) and longitudinal (below 3.5 cm from the anal verge, submitted to intersphincteric resection). The primary aim of this study was to evaluate the application of robotic surgery to the three types of bTME regarding the short and long-term oncological outcomes. Secondary aim was to identify survival prognostic factors for bTME rectal cancers. A total of 137 patients who underwent robotic-assisted bTME procedures between 2008 and 2018 were extracted from a prospectively collected database. Patient-related, operative and pathological factors were assessed. Morbidity was moderately high with 66% of patients reporting postoperative complications. Median follow up was 47 months (IQR, 31.5-66.5). Local recurrence rate was 15.3% with a statistical difference between the three types of bTME (p = 0.041). Disease progression/distant metastasis rate was 33.6%. Overall survival was significantly different (p = 0.023) with 1- and 3-years rates of: 77.8% and 55.0% (radial; n = 19); 96.6% and 84.8% (lateral; n = 30); 97.7% and 86.9% (longitudinal; n = 88). No statistical difference was observed for disease-free survival (p = 0.897). Local recurrence-free survival was significantly different between the groups (p = 0.031). Multivariate analysis showed that (y)pT (p = 0.028; HR (95% CI) 5.133 (1.192-22.097)), (y)pN (p = 0.014; HR (95% CI) 2.835 (1.240-6.482)) and type of bTME were associated to OS whilst (y)pT (p = 0.072) and type of bTME were not associated to LRFS.

A multicentre comparative study between laparoscopic and open surgery for intussusception in adults.

AIM: Intussusception in adults is rare and requires surgery in most cases. While abdominal laparoscopic surgery (LS) is becoming more popular, there are few reports on the outcomes of adult intussusception treated with LS. This study compared the feasibility of LS vs open surgery (OS) for adult intussusception. METHOD: We reviewed retrospectively the medical records of adult patients with intussusception from three tertiary hospitals between 2000 and 2016. The patients were divided into LS and OS groups, and their surgical outcomes were compared. RESULTS: Surgery was indicated in 71 patients with intussusception (41 LS and 30 OS). The median age of the patients was 49.0 and 51.5 years in the LS and OS groups, respectively (P = 0.930). Overall, nine (12.7%) patients had a negative laparotomy or laparoscopy with spontaneous reduction of the intussusception. Conversion to OS from LS was necessary in one patient (2.4%). The operative time and intra-operative and postoperative complication rates were not significantly different. However, there were more serious complications such as bowel perforation and major vessel injury in the LS group. The patients in the LS group had a shorter time to first food intake and hospital stay vs patients in the OS group (4.0 vs 6.0 days, P < 0.001, and 7.0 vs 10.5 days, P < 0.001, respectively). CONCLUSION: LS may be feasible for adult intussusception; there may be more severe intra-operative complications than in OS.

Use of real-world registry data: a hernia mesh example.

PURPOSE: Clinical performance of hernia mesh devices is poorly understood due to a lack of relevant clinical trial and real-world data (RWD). Registries offer a means to capture longitudinal data in real-world practice. This report highlights the need for data quality, completeness, and appropriate analysis methodology for more accurate and informed interpretation of RWE of medical devices. METHODS: Hernia mesh registry data were used to cross-tabulate the 30-day infection rate of patients who received one of four mesh types. RESULTS: Initial data review suggested lower infection rate for permanent mesh versus absorbable mesh. Additional registry RWD were factored into the analysis, providing more context in the interpretation of the results. CONCLUSIONS: High-quality registries can be used to generate real-world evidence (RWE) to support surveillance and other regulatory decisions.

Understanding the patient perspective after ventral hernia repair.

PURPOSE: More than 350,000 ventral hernia repairs are performed in the U.S. each year. However, long-term quality of life of patients living with hernia repair is less known. Follow-up using patient-reported outcomes (measures) is an important representation of the patient experience and can inform quality improvements of hernia treatments. This study aims to understand the patients' experience after ventral hernia repair, to enhance quality of care and long-term hernia treatment outcomes. METHODS: To better understand long-term outcomes of ventral hernia repair and to enhance an existing PRO tool, two rounds of semi-structured interviews and focus groups were conducted. In total, 22 patients who had ventral hernia repair were enrolled. The patient perspectives obtained were grouped into themes to inform the further development of the PRO tool. Data were transcribed and analyzed using atlas.ti and Microsoft Word. RESULTS: Ten major themes were identified in this analysis. Patients' quality of life was impacted by hernia repairs and hernia recurrences, including chronic pain, effects on daily activities and social relationships, and the challenge in finding new treatments. The lack of provider-patient communication and patient understanding of hernia repairs highlighted the need for providing patients with more comprehensive information regarding repair options and outcomes prior to surgery. CONCLUSION: PRO assessments and meaningful communications between the physician and the patient can provide a comprehensive benefit-risk assessment prior to surgery, and may also improve patient understanding of what to expect during recovery from surgery.

Emulsified polycolloid substrate biobarrier for benzene and petroleum-hydrocarbon plume containment and migration control - A field-scale study.

The objective of this field-scale study was to assess the effectiveness of applying an emulsified polycolloid substrate (EPS; containing cane molasses, soybean oil, and surfactants) biobarrier in the control and remediation of a petroleum-hydrocarbon plume in natural waters. An abandoned petrochemical manufacturing facility site was contaminated by benzene and other petroleum products due to a leakage from a storage tank. Because benzene is a petroleum hydrocarbon with a high migration ability, it was used as the target compound in the field-scale study. Batch partition and sorption experiment results indicated that the EPS to water partition coefficient for benzene was 232 mg/mg at 25 °C. This suggests that benzene had a higher sorption affinity to EPS, which decreased the benzene concentrations in groundwater. The EPS solution was pressure-injected into three remediation wells (RWs; 150 L EPS in 800 L groundwater). Groundwater samples were collected from an upgradient background well, two downgradient monitor wells (MWs), and the three RWs for analyses. EPS injection increased total organic carbon (TOC) concentrations (up to 786 mg/L) in groundwater, which also resulted in the formation of anaerobic conditions. An abrupt drop in benzene concentration (from 6.9 to below 0.04 mg/L) was observed after EPS supplementation in the RWs due to both sorption and biodegradation mechanisms. Results show that the EPS supplement increased total viable bacteria and enhanced bioremediation efficiency, which accounted for the observed decrease in benzene concentration. The first-order decay rate in RW1 increased from 0.003 to 0.023 d-1 after EPS application. Injection of EPS resulted in significant growth of indigenous bacteria, and 23 petroleum-hydrocarbon-degrading bacterial species were detected, which enhanced the in situ benzene biodegradation efficiency. Results demonstrate that the EPS biobarrier can effectively contain a petroleum-hydrocarbon plume and prevent its migration to downgradient areas, which reduces the immediate risk presented to downgradient receptors.

Genomic screening of Fabry disease in young stroke patients: the Taiwan experience and a review of the literature.

BACKGROUND AND PURPOSE: Fabry disease is an X-linked disease, and enzyme-based screening methods are not suitable for female patients. METHODS: In total, 1000 young stroke patients (18-55 years, 661 with ischaemic stroke and 339 with hypertensive intracerebral hemorrhage) were recruited. The Sequenom iPLEX assay was used to detect 26 Fabry related mutation genes. The frequency of Fabry disease in young stroke was reviewed and compared between Asian and non-Asian countries. RESULTS: Two male patients with ischaemic stroke were found to have a genetic mutation of IVS4+919G>A. There was no α-galactosidase A (GLA) gene mutation in female patients. The frequency in Asian stroke patients was 0.62% (male vs. female 0.63% vs. 0.58%) with 0.72% for ischaemic stroke and none for hemorrhagic stroke, compared to 0.88% (0.77% vs. 1.08%) with 0.83% for ischaemic stroke and 1.40% for hemorrhagic stroke reported in western countries. CONCLUSION: IVS4+919G>A is the GLA mutation in Taiwanese young ischaemic stroke patients. Fabry disease is more frequent among non-Asian patients compared to Asian patients.

Ab initio computer simulations of non-equilibrium radiation-induced cascades in amorphous Ge2Sb2Te5.

Ion irradiation corresponds to a process that involves the production of non-equilibrium cascades in the host material, and the atomistic modelling of such events in glasses is challenging. Here, non-equilibrium cascades in amorphous Ge2Sb2Te5 phase-change memory material have been investigated by means of first-principles molecular-dynamics simulations. A stochastic boundary-conditions approach is employed to treat the thermal nature of the cascades and drive the modelled system back to equilibrium in a natural way, while four different initial thermal-spike energies are considered. A comprehensive analysis of the cascade evolution is presented with respect to the kinetic profile and the dynamics of the cascade inside the glass structure. The modelling results show that the instantaneous maximum kinetic energy decays rapidly with time, and that the time-scale of the ballistic phase of the cascade inside the glass model is very short. The quality of the implemented approach is validated through a comparison of the calculated structure factor for the modelled glasses with experimental data from the literature. Analysis of the bonding for all the species in the glass structure highlights particular structural modifications in the connectivity of the amorphous network due to the simulated cascade.

Leukocytes as a reservoir of circulating oncogenic DNA and regulatory targets of tumor-derived extracellular vesicles.

Essentials Tumor-bearing mice were employed to follow oncogenic HRAS sequences in plasma, and blood cells. Cancer DNA accumulated in leukocytes above levels detected in exosomes, platelets and plasma. Extracellular vesicles and nucleosomes are required for uptake of tumor DNA by leukocytes. Uptake of tumor-derived extracellular vesicles by leukocytes triggers coagulant phenotype. SUMMARY: Background Tumor-derived extracellular vesicles (EVs) and free nucleosomes (NSs) carry into the circulation a wealth of cancer-specific, bioactive and poorly understood molecular cargoes, including genomic DNA (gDNA). Objective Here we investigated the distribution of extracellular oncogenic gDNA sequences (HRAS and HER2) in the circulation of tumor-bearing mice. Methods and Results Surprisingly, circulating leukocytes (WBCs), especially neutrophils, contained the highest levels of mutant gDNA, which exceeded the amount of this material recovered from soluble fractions of plasma, circulating EVs, platelets, red blood cells (RBCs) and peripheral organs, as quantified by digital droplet PCR (ddPCR). Tumor excision resulted in disappearance of the WBC-associated gDNA signal within 2-9 days, which is in line with the expected half-life of these cells. EVs and nucleosomes were essential for the uptake of tumor-derived extracellular DNA by neutrophil-like cells and impacted their phenotype. Indeed, the exposure of granulocytic HL-60 cells to EVs from HRAS-driven cancer cells resulted in a selective increase in tissue factor (TF) procoagulant activity and interleukin 8 (IL-8) production. The levels of circulating thrombin-antithrombin complexes (TAT) were markedly elevated in mice harboring HRAS-driven xenografts. Conclusions Myeloid cells may represent a hitherto unrecognized reservoir of cancer-derived, EV/NS-associated oncogenic gDNA in the circulation, and a possible novel platform for liquid biopsy in cancer. In addition, uptake of this material alters the phenotype of myeloid cells, induces procoagulant and proinflammatory activity and may contribute to systemic effects associated with cancer.

"Snowmelt Sign" and "Corkscrew Microvessels" Predicting Epithelium Regeneration After Acute Rejection of Small-Bowel Transplantation: A Case Report.

Intestinal failure characterized by inadequate maintenance of nutrition via normal intestinal function comprises a group of disorders with many different causes. If parenteral nutrition dependency develops, which is associated with higher mortality and complications, it is considered for intestine transplantation. However, the graft failure rate is not low, and acute cellular rejection is one of the most important reasons for graft failure. As a result, early identification of rejection and timely modification of anti-rejection medications have been considered to be associated with better graft and patient survival rates. The diagnostic gold standard for rejection is mainly based on histology, but hours of delay by pathology may occur. Some researchers investigated the association of endoscopic images with graft rejection to provide timely diagnosis. In this study, we present the first case report with characteristic features under magnifying endoscopy with a narrow-band imaging system to predict epithelial regeneration and improvement of graft rejection in a patient with small-bowel transplantation.

Caveolin-1 serves as a negative effector in senescent human gingival fibroblasts during Fusobacterium nucleatum infection.

It is well established that aging is associated with increased susceptibility to infectious diseases. Fusobacterium nucleatum is a well-known bacterial species that plays a central bridging role between early and late colonizers in the human oral cavity. Further, the ability of F. nucleatum to invade gingival fibroblasts (GFs) is critical to the development of periodontal diseases. However, the mechanisms underlying the age-related infection of GFs by F. nucleatum remain unknown. We used young (fourth passage) and senescent (22nd passage) GFs to investigate the mechanisms of F. nucleatum infection in aged GFs and first observed increased invasion of F. nucleatum in senescent GFs. We also found that the co-localization of caveolin-1 (Cav-1), a protein marker of aging, with F. nucleatum and the knockdown of Cav-1 in GFs reduced F. nucleatum invasion. Additionally, F. nucleatum infection triggered the production of reactive oxygen species (ROS) through activation of NADPH oxidase in GFs, but senescent GFs exhibited significantly lower levels of NADPH oxidase activity and ROS production compared with young GFs in both the uninfected and infected conditions. Also, senescent GFs exhibited a decline in proinflammatory cytokine production and extracellular signal regulated kinase (ERK) phosphorylation following F. nucleatum infection. Interestingly, the knockdown of Cav-1 in senescent GFs increased NADPH oxidase activity and caused the upregulation of interleukin-6 and interleukin-8 and the phosphorylation of ERK. Collectively, the increased expression of Cav-1 might play a critical role in F. nucleatum invasion and could hinder the host response in senescent GFs.

MRI audit of complications in intracranial stenosis treated with Wingspan device.

OBJECTIVES: To evaluate the safety and efficacy of the Wingspan device for the treatment of symptomatic intracranial atherosclerotic stenosis (ICAS). METHODS: We audited a prospective ongoing database of consecutive patients who received Wingspan stenting between January 2013 and December 2015. All patients underwent MRI to audit any complications during the early follow-up period. We focused on the clinical demographics, lesion characteristics, treatment results, and periprocedural complications. Functional outcomes were measured with the modified Rankin Scale (mRS) at discharge and after 3 months. RESULTS: Intracranial stenting was performed in 50 patients (100%). Mean stenosis pre-stenting was 76.5±13.1% and post-stenting residual stenosis was 19.8±13.8%. The overall 30-day rate of procedure-related complications was 6.0% (3/50). Two patients (4%) developed in-stent restenosis, one of whom had a dissection at the middle cerebral artery. Interestingly, on the follow-up MRI scan there was a high incidence of asymptomatic diffusion-weighted imaging (DWI) hyperintensities, 46% (23/50) presumed to be due to microembolic causes. At the 90-day, 180-day, and 1-year follow-up, three patients had further strokes resulting in a total complication rate of 12%. 92% had excellent outcomes (mRS 0-1) and only one patient had deterioration of his mRS score. CONCLUSIONS: ICAS treated by Wingspan stenting using pre-placement balloon angioplasty appears safe and effective with a high technical success rate and favorable outcomes. There is a high incidence of asymptomatic DWI hyperintensites post-procedure, but these do not appear to result in long-term sequelae.

Intentional examination of esophagus by narrow-band imaging endoscopy increases detection rate of cervical inlet patch.

Foci of heterotopic gastric mucosa have been identified at different sites in the human body and the most common location is the proximal esophagus which is referred to as cervical inlet patch (CIP). The true prevalence of CIP varies and it is usually incidental findings during endoscopy. Because CIP is always asymptomatic, it was believed to be of little clinical relevance. However, emerging studies have described the acid-secreting characteristics of heterotopic gastric mucosa and associations of CIP with gastroesophageal reflux disease (GERD). In addition, complications such as stricture, fistula, infection, mucosal hyperplasia, and malignant transformation have been reported. In this study, we investigated the prevalence of CIP, its associations with clinical manifestations, and the effect of intentional screening upper esophagus by magnifying endoscopy-narrow-band imaging (ME-NBI) system. Consecutive healthy adults who underwent panendoscopy were separated into two groups. Patients in group I (n = 471) were examined by an endoscopist who intended to find CIPs by ME-NBI. Patients in group II (n = 428) were examined by two endoscopists who were unaware of the study and performed white-light imaging endoscopy. Participants provided questionnaires on GERD-related symptoms. Higher CIP prevalence (11.7% vs. 1.9%, P < 0.0001) and longer duration of esophageal examination (mean ± standard deviation, 17.50 ± 12.40 vs. 15.24 ± 10.78 seconds, P = 0.004) were noted in group I than in group II. Analyzing group I patients revealed the higher prevalences of reflux symptoms (32.7% vs. 18.3%, P = 0.013) and erosive esophagitis (43.6% vs. 25.5%, P = 0.005) in patients with CIP than in those without. CIP was not associated with globus or dysphagia symptoms. More small CIPs (< 5 mm) were detected by ME-NBI than by white-light imaging (85.3% vs. 41.4%, P = 0.001). In conclusion, CIP prevalence was not low under intentional ME-NBI examination of the upper esophagus. The clinical relevance of CIP and its association with GERD require further investigation.

Staging accuracy of endoscopic ultrasound performed by nonexpert endosonographers in patients with resectable esophageal squamous cell carcinoma: is it possible?

The accuracy of endoscopic ultrasound (EUS) is operator-dependent. According to learning curve study, the accuracy of EUS T-staging for esophageal cancer has been reported to be greater in an investigator who had performed at least 100 EUS examinations. We determined comparative study regarding T-staging accuracy of EUS for esophageal squamous cell carcinoma between expert and nonexpert endoscopic ultrasonographers. We retrospectively identified 73 consecutive patients with esophageal squamous cell carcinoma who underwent EUS and endoscopic mucosal resection, endoscopic submucosal dissection, or surgery. EUS was performed by expert (Group 1) and nonexpert (Group 2) endoscopic ultrasonographers in multitertiary hospitals. Groups 1 and 2 were 37 and 36 patients during 2005-2011, respectively. Forty-two patients (57.5%) of the overall patients underwent surgical exploration. Correct endoscopic ultrasonographic T-staging of Group 1 was observed in 34 (91.9%) patients, while that of Group 2 was observed in 26 (72.2%) patients. And there was significant difference in correct endoscopic ultrasonographic T-staging between Group 1 and Group 2 (P = 0.035). The incorrect endoscopic ultrasonographic T-staging of Group 1 were three cases that were overstaging (8.1%), but in Group 2 there were seven overstaging (19.4%) and three understaging (8.3%). There was no significant difference in overstaging or understaging of incorrect endoscopic ultrasonographic T-staging between Group 1 and Group 2 (P = 0.528). This study first provides evidence that endoscopic ultrasonographic T-staging of nonexpert endoscopic ultrasonographers was inferior to be correct, compared with that of expert endoscopic ultrasonographers. EUS staging for esophageal cancer should be performed by expert endoscopic ultrasonographers to provide appropriate management strategy.

Death-associated protein kinase 1 has a critical role in aberrant tau protein regulation and function.

The presence of tangles composed of phosphorylated tau is one of the neuropathological hallmarks of Alzheimer's disease (AD). Tau, a microtubule (MT)-associated protein, accumulates in AD potentially as a result of posttranslational modifications, such as hyperphosphorylation and conformational changes. However, it has not been fully understood how tau accumulation and phosphorylation are deregulated. In the present study, we identified a novel role of death-associated protein kinase 1 (DAPK1) in the regulation of the tau protein. We found that hippocampal DAPK1 expression is markedly increased in the brains of AD patients compared with age-matched normal subjects. DAPK1 overexpression increased tau protein stability and phosphorylation at multiple AD-related sites. In contrast, inhibition of DAPK1 by overexpression of a DAPK1 kinase-deficient mutant or by genetic knockout significantly decreased tau protein stability and abolished its phosphorylation in cell cultures and in mice. Mechanistically, DAPK1-enhanced tau protein stability was mediated by Ser71 phosphorylation of Pin1, a prolyl isomerase known to regulate tau protein stability, phosphorylation, and tau-related pathologies. In addition, inhibition of DAPK1 kinase activity significantly increased the assembly of MTs and accelerated nerve growth factor-mediated neurite outgrowth. Given that DAPK1 has been genetically linked to late onset AD, these results suggest that DAPK1 is a novel regulator of tau protein abundance, and that DAPK1 upregulation might contribute to tau-related pathologies in AD. Therefore, we offer that DAPK1 might be a novel therapeutic target for treating human AD and other tau-related pathologies.