Barrett's esophagus (BE) is the precursor to esophageal adenocarcinoma (EAC). Progression to cancer typically occurs in a stepwise fashion through worsening dysplasia and ultimately, invasive neoplasia. Established EAC with deep involvement of the esophageal wall and/or metastatic disease is invariably associated with poor long-term survival rates. This guides the rationale of surveillance of Barrett’s in an attempt to treat lesions at an earlier, and potentially curative stage. The last two decades have seen a paradigm shift in management of Barrett’s with rapid expansion in the role of endoscopic eradication therapy (EET) for management of dysplastic and early neoplastic BE, and there have been substantial changes to international consensus guidelines for management of early BE based on evolving evidence. This review aims to assist the physician in the therapeutic decision-making process with patients by comprehensive review and summary of literature surrounding natural history of Barrett’s by histological stage, and the effectiveness of interventions in attenuating the risk posed by its natural history. Key findings were as follows. Non-dysplastic Barrett’s is associated with extremely low risk of progression, and interventions cannot be justified. The annual risk of cancer progression in low grade dysplasia is between 1%-3%; EET can be offered though evidence for its benefit remains confined to highly select settings. High-grade dysplasia progresses to cancer in 5%-10% per year; EET is similarly effective to and less morbid than surgery and should be routinely performed for this indication. Risk of nodal metastases in intramucosal cancer is 2%-4%, which is comparable to operative mortality rate, so EET is usually preferred. Submucosal cancer is associated with nodal metastases in 14%-41% hence surgery remains standard of care, except for select situations. 相似文献
Minimally invasive approaches are increasingly being applied in surgeries and have recently been used in living donor hepatectomy. We have developed a safe and reproducible method for minimally invasive living donor liver transplantation, which consists of pure laparoscopic explant hepatectomy and pure laparoscopic implantation of the graft, which was inserted through a suprapubic incision. Pure laparoscopic explant hepatectomy without liver fragmentation was performed in a 60-year-old man with alcoholic liver cirrhosis and hepatocellular carcinoma. The explanted liver was retrieved through a suprapubic incision. A modified right liver graft, procured from his 24-year-old son using the pure laparoscopic method, was inserted through a suprapubic incision, and implantation was performed intracorporeally throughout the procedure. The time required to remove the liver was 369 min, and the total operative time was 960 min. No complications occurred during or after the surgery. The patient recovered well, and his hospital stay was of 11 days. Pure laparoscopic living donor liver transplantation from explant hepatectomy to implantation was performed successfully. It is a feasible procedure when performed by a highly experienced surgeon and transplantation team. Further studies with larger sample sizes are needed to confirm its safety and feasibility.
Journal of Immigrant and Minority Health - Little attention has been paid to online health information seeking (OHIS) among immigrants residing in rural areas. This study examines the intensity of... 相似文献
Early stage localized prostate cancer (PCa) has an excellent prognosis; however, patient survival drops dramatically when PCa metastasizes. The molecular mechanisms underlying PCa metastasis are complex and remain unclear. Here, we examine the role of a new member of the fatty acid‐binding protein (FABP) family, FABP12, in PCa progression. FABP12 is preferentially amplified and/or overexpressed in metastatic compared to primary tumors from both PCa patients and xenograft animal models. We show that FABP12 concurrently triggers metastatic phenotypes (induced epithelial‐to‐mesenchymal transition (EMT) leading to increased cell motility and invasion) and lipid bioenergetics (increased fatty acid uptake and accumulation, increased ATP production from fatty acid β‐oxidation) in PCa cells, supporting increased reliance on fatty acids for energy production. Mechanistically, we show that FABP12 is a driver of PPARγ activation which, in turn, regulates FABP12''s role in lipid metabolism and PCa progression. Our results point to a novel role for a FABP‐PPAR pathway in promoting PCa metastasis through induction of EMT and lipid bioenergetics.
Abbreviations
AR
androgen receptor
ATP
adenosine triphosphate
CN
copy number
CPT1
carnitine palmitoyltransferase I
CS
citrate synthase
EMT
epithelial–mesenchymal transition
ET
electron transfer‐state
FABP
fatty acid‐binding protein
LD
lipid droplet
OA
oleic acid
PCa
prostate cancer
PPAR
peroxisome proliferator‐activated receptor
PPRE
peroxisome proliferator‐activated receptor response element
The purpose of the study was to compare cancer detection rates between 12-core transrectal ultrasound-guided prostate biopsy (TRUS-Bx) and multiparametric magnetic resonance imaging (mpMRI)-guided target prostate biopsy (MRI-TBx) according to prostate-specific antigen (PSA) level in biopsy-naive patients.
Patients and Methods
A retrospective study was conducted in 2009 biopsy-naive patients with suspected prostate cancer (PSA ≤20 ng/mL). Patients underwent TRUS-Bx (n = 1786) or MRI-guided target prostate biopsy (MRI-TBx; n = 223) from September 2013 to March 2017 and were stratified according to each of 4 PSA cutoffs. MRI-TBx was performed on lesions with Prostate Imaging Reporting and Data System (PI-RADS) scores of 3 to 5 on mpMRI. Clinically significant prostate cancer (csPCa) was defined as Gleason ≥7. Propensity score matching was performed using the prebiopsy variables, which included age, PSA, prostate volume, and PSA density.
Results
Propensity score matching resulted in 222 patients in each group. There were significant differences between the TRUS-Bx and MRI-TBx groups in the overall detection rates of prostate cancer (41.4% vs. 55.4%; P = .003) and csPCa (30.1% vs. 42.8%; P = .005). However, across PSA cutoffs, MRI-TBx detected more prostate cancer than TRUS-Bx at PSA levels of 2.5 to <4 (29.5% vs. 56.6%; P < .001). The csPCa detection rates of TRUS-Bx and MRI-TBx did not differ significantly within the PSA cutoffs. There was a significantly higher detection rate of prostate cancer and csPCa in lesions with PI-RADS scores 4 and 5 than in those with a score of 3.
Conclusion
Prebiopsy mpMRI and subsequent targeted biopsy had a higher detection rate than TRUS-Bx in patients with prostate cancer and csPCa. 相似文献
Journal of Neurology - To define the prevalence and characteristics of single ocular motor nerve palsy (OMNP) associated with positive serum anti-GQ1b antibody. We performed a prospective... 相似文献
The associations of long-term exposure to particulate matter <10 μm in size (PM10), nitrogen dioxide (NO2), carbon monoxide (CO), sulfur dioxide (SO2), and ozone (O3) with cardiometabolic diseases (CMD) remain uncertain in the Korean population. Therefore, we sought to examine the associations between PM10, NO2, CO, SO2, and O3 and CMD using data collected from the Korean Community Health Survey.
Methods and results
We selected 100,867 adults aged 19 years or older who had lived in the same domicile for ≥10 years and surveyed them to collect data on socioeconomic characteristics; health-related behaviors; obesity; and physician-diagnosed CMD history, including hypertension, diabetes mellitus, dyslipidemia, stroke, myocardial infarction, and ischemic heart disease. We calculated interquartile ranges for PM10, NO2, CO, SO2, and O3 from the 10 year average concentrations (2003–2012). Hypertension, diabetes mellitus, and dyslipidemia were positively associated with PM10, NO2, CO, SO2, and O3 after adjusting for confounding factors. Obesity was positively associated with PM10, NO2, SO2, and O3. On the other hand, we found no associations between stroke, myocardial infarction, and ischemic heart disease and exposure to PM10, NO2, CO, SO2, and O3 in these subjects. In subjects aged ≥65 years, the risk of dyslipidemia was markedly increased under exposure to NO2 and CO compared to subjects aged <65 years. The risk of obesity was also significantly increased under exposure to PM10 and NO2. However, sex differences in these associations were not found.
Conclusion
Long-term exposure to PM10, NO2, CO, SO2, and O3 may be a risk factor of CMD in Korean adults. 相似文献
Patient selection for open lower extremity revascularization in patients with chronic kidney disease (CKD) remains a clinical challenge. This study investigates the impact of CKD on early graft failure, postoperative complications, and mortality in patients undergoing lower extremity bypass for critical limb ischemia.
Methods
The National Surgical Quality Improvement Program database was queried for all patients with critical limb ischemia from 2012 to 2015 who underwent lower extremity bypass using the targeted vascular set. The glomerular filtration rate was calculated using the Chronic Kidney Disease Epidemiology Collaboration Study equation. CKD categories were determined from the National Kidney Foundation Kidney Disease Outcomes Quality Initiative staging criteria. Patients were classified into three groups: CKD stages 3 or lower (mild to moderate CKD), CKD stages 4 or 5 (severe CKD), and on hemodialysis (HD). Multiple variable analysis was used to examine graft failure, mortality, and postoperative complications.
Results
The Surgical Quality Improvement Program database identified 6978 patients who underwent infrainguinal lower extremity arterial bypass during the study period. There were 6101 patients (87.4%) with mild to moderate CKD, 327 (4.7%) with severe CKD, and 550 (7.9%) on HD. Patients with severe CKD and on HD were more likely to have revascularization for tissue loss (54.9% vs 68.8% and 74.7%; P < .01). Patients with severe CKD and those on HD had higher rates of early graft failure, postoperative myocardial infarction, and rates of reoperation. Multiple variable analysis confirmed these results showing that HD was associated with postoperative myocardial infarction, readmission, and increased mortality. It also demonstrated that severe CKD was associated with graft failure (odds ratio [OR], 1.67; 95% confidence interval [CI], 1.12-2.50; P = .01), postoperative myocardial infarction (OR, 2.16; 95% CI, 1.35-3.45; P < .01), and readmission (OR, 1.38; 95% CI, 1.06-1.80; P = .02). Other factors associated with graft failure include functional status (OR, 1.39; 95% CI, 1.08-1.80; P = .01), African American race (OR, 1.72; 95% CI, 1.39-2.13; P < .01), and distal bypass (OR, 1.33; 95% CI, 1.09-1.61; P < .01).
Conclusions
CKD is a significant predictor of perioperative morbidity after lower extremity bypass. Patients with severe CKD have worse postoperative outcomes without increased mortality. Those on HD have worse survival and postoperative outcomes. 相似文献
Rosacea is a chronic inflammatory skin condition whose etiology has been linked to mast cells and the antimicrobial peptide cathelicidin LL-37. Individuals with refractory disease have demonstrated clinical benefit with periodic injections of onabotulinum toxin, but the mechanism of action is unknown.
Objectives
To investigate the molecular mechanism by which botulinum toxin improves rosacea lesions.
Methods
Primary human and murine mast cells were pretreated with onabotulinum toxin A or B or control. Mast cell degranulation was evaluated by β-hexosaminidase activity. Expression of botulinum toxin receptor Sv2 was measured by qPCR. The presence of SNAP-25 and VAMP2 was established by immunofluorescence. In vivo rosacea model was established by intradermally injecting LL-37 with or without onabotulinum toxin A pretreatment. Mast cell degranulation was assessed in vivo by histologic counts. Rosacea biomarkers were analyzed by qPCR of mouse skin sections.
Results
Onabotulinum toxin A and B inhibited compound 48/80-induced degranulation of both human and murine mast cells. Expression of Sv2 was established in mouse mast cells. Onabotulinum toxin A and B increased cleaved SNAP-25 and decreased VAMP2 staining in mast cells respectively. In mice, injection of onabotulinum toxin A significantly reduced LL-37-induced skin erythema, mast cell degranulation, and mRNA expression of rosacea biomarkers.
Conclusions
These findings suggest that onabotulinum toxin reduces rosacea-associated skin inflammation by directly inhibiting mast cell degranulation. Periodic applications of onabotulinum toxin may be an effective therapy for refractory rosacea and deserves further study. 相似文献
