Summary Background Current staging methods do not accurately predict the risk of disease recurrence and benefit of adjuvant chemotherapy for patients who have had surgery for stage II colon cancer. ...We postulated that expression patterns of multiple microRNAs (miRNAs) could, if combined into a single model, improve postoperative risk stratification and prediction of chemotherapy benefit for these patients. Method Using miRNA microarrays, we analysed 40 paired stage II colon cancer tumours and adjacent normal mucosa tissues, and identified 35 miRNAs that were differentially expressed between tumours and normal tissue. Using paraffin-embedded specimens from a further 138 patients with stage II colon cancer, we confirmed differential expression of these miRNAs using qRT-PCR. We then built a six-miRNA-based classifier using the LASSO Cox regression model, based on the association between the expression of every miRNA and the duration of individual patients' disease-free survival. We validated the prognostic and predictive accuracy of this classifier in both the internal testing group of 138 patients, and an external independent group of 460 patients. Findings Using the LASSO model, we built a classifier based on the six miRNAs: miR-21-5p, miR-20a-5p, miR-103a-3p, miR-106b-5p, miR-143-5p, and miR-215. Using this tool, we were able to classify patients between those at high risk of disease progression (high-risk group), and those at low risk of disease progression (low-risk group). Disease-free survival was significantly different between these groups in every set of patients. In the initial training group of patients, 5-year disease-free survival was 89% (95% CI 77·3–94·4) for the low-risk group, and 60% (46·3–71·0) for the high-risk group (hazard ratio HR 4·24, 95% CI 2·13–8·47; p<0·0001). In the internal testing set of patients, 5-year disease-free survival was 85% (95% CI 74·3–91·8) for the low-risk group, and 57% (42·8–68·5) for the high-risk group (HR 3·63, 1·86–7·01; p<0·0001), and in the independent validation set of patients, was 85% (79·6–89·0) for the low-risk group and 54% (46·4–61·1) for the high-risk group (HR 3·70, 2·56–5·35; p<0·0001). The six-miRNA-based classifier was an independent prognostic factor for, and had better prognostic value than, clinicopathological risk factors and mismatch repair status. In an ad-hoc analysis, the patients in the high-risk group were found to have a favourable response to adjuvant chemotherapy (HR 1·69, 1·17–2·45; p=0·0054). We developed two nomograms for clinical use that integrated the six-miRNA-based classifier and four clinicopathological risk factors to predict which patients might benefit from adjuvant chemotherapy after surgery for stage II colon cancer. Conclusion Our six-miRNA-based classifier is a reliable prognostic and predictive tool for disease recurrence in patients with stage II colon cancer, and might be able to predict which patients benefit from adjuvant chemotherapy. It might facilitate patient counselling and individualise management of patients with this disease. Funding Natural Science Foundation of China.
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.
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.
Summary Background The prevalence of chronic kidney disease is high in developing countries. However, no national survey of chronic kidney disease has been done incorporating both estimated ...glomerular filtration rate (eGFR) and albuminuria in a developing country with the economic diversity of China. We aimed to measure the prevalence of chronic kidney disease in China with such a survey. Methods We did a cross-sectional survey of a nationally representative sample of Chinese adults. Chronic kidney disease was defined as eGFR less than 60 mL/min per 1·73 m2 or the presence of albuminuria. Participants completed a lifestyle and medical history questionnaire and had their blood pressure measured, and blood and urine samples taken. Serum creatinine was measured and used to estimate glomerular filtration rate. Urinary albumin and creatinine were tested to assess albuminuria. The crude and adjusted prevalence of indicators of kidney damage were calculated and factors associated with the presence of chronic kidney disease analysed by logistic regression. Findings 50 550 people were invited to participate, of whom 47 204 agreed. The adjusted prevalence of eGFR less than 60 mL/min per 1·73 m2 was 1·7% (95% CI 1·5–1·9) and of albuminuria was 9·4% (8·9–10·0). The overall prevalence of chronic kidney disease was 10·8% (10·2–11·3); therefore the number of patients with chronic kidney disease in China is estimated to be about 119·5 million (112·9–125·0 million). In rural areas, economic development was independently associated with the presence of albuminuria. The prevalence of chronic kidney disease was high in north (16·9% 15·1–18·7) and southwest (18·3% 16·4–20·4) regions compared with other regions. Other factors independently associated with kidney damage were age, sex, hypertension, diabetes, history of cardiovascular disease, hyperuricaemia, area of residence, and economic status. Interpretation Chronic kidney disease has become an important public health problem in China. Special attention should be paid to residents in economically improving rural areas and specific geographical regions in China. Funding The Ministry of Science and Technology (China); the Science and Technology Commission of Shanghai; the National Natural Science Foundation of China; the Department of Health, Jiangsu Province; the Sichuan Science and Technology Department; the Ministry of Education (China); the International Society of Nephrology Research Committee; and the China Health and Medical Development Foundation.
Abstract Background Laparoscopic colorectal resection has been gaining popularity over the past two decades. However, studies about laparoscopic rectal surgery in elderly patients with long-term ...oncologic outcomes are limited. In this study, we evaluated the short-term and long-term outcomes of laparoscopic and open resection in patients with rectal cancer aged ≥70 y. Methods From 2007–2012, a total of 294 consecutive patients with rectal cancer from a single institution were included, 112 patients undergoing laparoscopic rectal resection were compared with 182 patients undergoing open rectal resection. Results Seven (6.3%) patients in the laparoscopic group required conversion to open surgery. The two groups were well balanced in terms of age, gender, body mass index, American society of anesthesiologists scores, site, and stage of the tumors. Laparoscopic surgery was associated with significantly longer median operating time (220 versus 200 min; P = 0.005), less estimated blood loss (100 versus 150 mL; P < 0.001), a shorter postoperative hospital stay (8 versus 11 d), lower overall postoperative complication rate (15.2% versus 26.4%; P = 0.025), wound-related complication rate (7.14% versus 17.03%; P = 0.015), less need of blood transfusion (8.04% versus 16.5%; P = 0.038), and surgical intensive care unit after surgery (12.5% versus 22.0%; P = 0.042) when compared with open surgery. Mortality, quality of surgical specimen, lymph nodes harvested, positive distal, and circumferential margin rate were not significantly different between two groups. The estimated 3-y survival rates were similar between two groups. Conclusions Laparoscopic rectal surgery is safe and feasible in patients >70 y and is associated with better short-term outcomes when compared with open surgery.
Abstract Background A history of previous abdominal surgery (PAS) may increase the complexity of laparoscopic colorectal surgery. The aim of this study was to investigate the impact of PAS on the ...outcomes of laparoscopic colorectal resection for colorectal cancer. Methods A total of 378 colorectal cancer patients (group A) with a history of PAS were 1:1 matched to 378 controls (group B) without PAS from our prospective laparoscopic colorectal surgery database. The two groups were matched for age, gender, body mass index, American Society of Anesthesiology score, tumor location, type of surgical procedure, and tumor stage. Results Patients in the two groups were well balanced with respect to baseline demographic and clinical characteristics. Group A was associated with significantly longer median operating time (220 versus 200 min; P = 0.002). Conversion rate in group A (63/378, 16.67%) was almost twice as high as that in group B (36/378, 9.55%; P = 0.004). Conversions caused by adhesion were more common in patients with a history of PAS (55.56% 35/63 versus 27.78% 10/36, P = 0.008). Postoperative recovery time, length of postoperative hospital stay, perioperative mortality and morbidity rate, lymph nodes harvested, circumferential resection margin positive rate, 3-y disease-free survival, and overall survival rate were not significantly different between the two groups. Conclusions Laparoscopic colorectal surgery for colorectal cancer patients with PAS is time consuming, but the incidence of a successfully completed laparoscopic colorectal resection remains high, and the short- and long-term outcomes are not affected by PAS.
OBJECTIVE To assess whether the relationship between abnormal fasting plasma glucose (FPG) levels and patient outcomes holds for both older men and older women with acute myocardial infarction (AMI). ...PATIENTS AND METHODS From April 1, 2004, to October 31, 2006, a total of 2016 consecutive older patients (age ≥65 years) presenting with AMI were screened. Of these patients, 1854 were consecutively enrolled in the study. Patients were categorized into 4 groups: the hypoglycemic group (FPG, ≤90.0 mg/dL to convert to mmol/L, multiply by 0.0555; n=443, 23.9%), the euglycemic group (FPG, 90.1-126.0 mg/dL; n=812, 43.8%), the mildly hyperglycemic group (FPG, 126.1-162.0 mg/dL; n=308, 16.6%), and the severely hyperglycemic group (FPG, ≥162.1 mg/dL; n=291, 15.7%). The primary outcomes were rates of in-hospital and 3-year mortality. RESULTS Female patients were older and had a higher incidence of diabetes mellitus but lower rates of smoking and use of invasive therapy. Men tended to have a higher frequency of hypoglycemia, whereas women tended to have a higher frequency of hyperglycemia. No significant difference was found in in-hospital (10.9% vs 9.1%; P =.36) or 3-year (24.5% vs 24.5%; P =.99) mortality between male and female patients, and FPG-associated mortality did not vary significantly by sex. CONCLUSION An increased FPG level was associated with a relatively higher risk of in-hospital mortality in men but not in women. Nonetheless, increased and decreased FPG levels at admission could predict higher mortality rates regardless of sex. There was a striking U-shaped relationship between FPG levels and in-hospital and 3-year mortality. The effect of abnormal FPG level on outcomes among older patients with AMI did not vary significantly by sex.
Objectives This study explored the novel strategy of hypoxic preconditioning of bone marrow mesenchymal stem cells before transplantation into the infarcted heart to promote their survival and ...therapeutic potential of mesenchymal stem cell transplantation after myocardial ischemia. Methods Mesenchymal stem cells from green fluorescent protein transgenic mice were cultured under normoxic or hypoxic (0.5% oxygen for 24 hours) conditions. Expression of growth factors and anti-apoptotic genes were examined by immunoblot. Normoxic or hypoxic stem cells were intramyocardially injected into the peri-infarct region of rats 30 minutes after permanent myocaridal infarction. Death of mesenchymal stem cells was assessed in vitro and in vivo after transplantation. Angiogenesis, infarct size, and heart function were measured 6 weeks after transplantation. Results Hypoxic preconditioning increased expression of pro-survival and pro-angiogenic factors including hypoxia-inducible factor 1, angiopoietin-1, vascular endothelial growth factor and its receptor, Flk-1, erythropoietin, Bcl-2, and Bcl-xL. Cell death of hypoxic stem cells and caspase-3 activation in these cells were significantly lower compared with that in normoxic stem cells both in vitro and in vivo. Transplantation of hypoxic versus normoxic mesenchymal stem cells after myocardial infarctiion resulted in an increase in angiogenesis, as well as enhanced morphologic and functional benefits of stem cell therapy. Conclusions Hypoxic preconditioning enhances the capacity of mesenchymal stem cells to repair infarcted myocardium, attributable to reduced cell death and apoptosis of implanted cells, increased angiogenesis/vascularization, and paracrine effects.
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