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.
Summary Primary mammary neuroendocrine carcinoma (NEC) is an uncommon entity that accounts for 2% to 5% of breast carcinomas. Recent reports have shown that NEC of the breast is an aggressive subtype ...of mammary carcinoma that is distinct from invasive ductal carcinoma, not otherwise specified, and have suggested that these tumors have a poorer prognosis than invasive ductal carcinoma, not otherwise specified. In this study, we provide the first cytogenetic characterization of mammary NEC using both conventional G-banding and spectral karyotype on a group of 7 tumors. We identified clonal chromosomal aberrations in 5 (71.4%) cases, with 4 of them showing complex karyotypes. Of these, recurrent numerical aberrations included gain of chromosome 7 (n = 2) and loss of chromosome 15 (n = 2). Recurrent clonal structural chromosomal aberrations involved chromosomes 1 (n = 3), 3 (n = 2), 6q (n = 3), and 17q (n = 3). Of the 4 (57.1%) cases with complex karyotypes, 2 showed evidence of chromothripsis, a phenomenon in which tens to hundreds of genomic rearrangements occur in a one-off cellular crisis. One of these had evidence of chromothripsis involving chromosomes 1, 6, 8, and 15. The other also had evidence of chromosome 8 chromothripsis, making this a recurrent finding shared by both cases. We also found that mammary NEC shared some cytogenetic abnormalities—such as trisomy 7 and 12—with other neuroendocrine tumors in the lung and gastrointestinal tract, suggesting trisomy 7 and 12 as potential common molecular aberrations in neuroendocrine tumors. To our knowledge, this is the first report on molecular cytogenetic characterization of mammary NEC.
Thoracoscopic anatomic pulmonary segmentectomy and subsegmentectomy have become sophisticated surgical solutions for complex pulmonary diseases. The rapid development of three-dimensional computed ...tomographic angiography (3DCTA) has made it possible to provide more refined individualized anatomic details and has consequently enabled subsubsegmentectomy (SSS). In this study, we report two successful thoracoscopic anatomic SSSs of the left S1+2 aii and S3 aii under the guidance of 3DCTA reconstructed images. To the best of our knowledge, these are the first two cases of SSSs ever detailed reported. The nomenclature of subsubsegments is adopted according to the Japanese Committee on the Nomenclature for Bronchial Branching.
Background Obsessive–compulsive disorder (OCD) is a common, heritable neuropsychiatric disorder, hypothetically underpinned by dysfunction of brain cortical-striatal-thalamic-cortical (CSTC) ...circuits; however, the extent of brain functional abnormalities in individuals with OCD is unclear, and the genetic basis of this disorder is poorly understood. We determined the whole brain functional connectivity patterns in patients with OCD and their healthy first-degree relatives. Methods We used resting-state fMRI to measure functional connectivity strength in patients with OCD, their healthy first-degree relatives and healthy controls. Whole brain functional networks were constructed by measuring the temporal correlations of all brain voxel pairs and further analyzed using a graph theory approach. Results We enrolled 39 patients with OCD, 20 healthy first-degree relatives and 39 healthy controls in our study. Compared with healthy controls, patients with OCD showed increased functional connectivity primarily within the CSTC circuits and decreased functional connectivity in the occipital cortex, temporal cortex and cerebellum. Moreover, patients with OCD and their first-degree relatives exhibited overlapping increased functional connectivity strength in the bilateral caudate nucleus, left orbitofrontal cortex (OFC) and left middle temporal gyrus. Limitations Potential confounding factors, such as medication use, heterogeneity in symptom clusters and comorbid disorders, may have impacted our findings. Conclusion Our preliminary results suggest that patients with OCD have abnormal resting-state functional connectivity that is not limited to CSTC circuits and involves abnormalities in additional large-scale brain systems, especially the limbic system. Moreover, resting-state functional connectivity strength abnormalities in the left OFC, bilateral caudate nucleus and left middle temporal gyrus may be neuroimaging endophenotypes for OCD.
Abstract Background Acute-on-chronic liver failure (ACLF) is a severe clinical condition for which liver transplantation (LT) is the only curative option. However, there are little published data on ...risk factors and outcomes of LT for ACLF. Methods The objective of this study was to analyze preoperative, intraoperative, postoperative, and overall survival data on 100 consecutive cases with ACLF in order to try to determine for which patients LT are futile. Results One hundred consecutive patients with pathology-confirmed ACLF who underwent LT from June 2004 to September 2012 were enrolled. The preoperative data showed that all patients were in a serious condition with a median high model for end-stage liver disease (MELD) score of 32, total bilirubin of 440.20 umol/L, international normalized ratio (INR) of 3.012, and at least one organ dysfunction as assessed by a Sequential Organ Failure Assessment (SOFA) score of ≥9. The patients had either deceased or a living donor LT with an overall mortality of 20%. The 1-, 3-, and 5-year cumulative survival rates were 76.8%, 75.6%, and 74.1%, respectively, and graft 1-, 3-, and 5-y accumulative survival rates were 73.3%, 72.1%, and 70.6%, respectively. However, the area under receiver operating characteristic of SOFA score, MELD score, as well as Child-Pugh score were 0.552, 0.547, and 0.547, respectively. Conclusions Both deceased and living donor LT are effective therapeutic options for patients with ACLF and the short- and long-term survival rates are encouraging. It is important to conduct more prospective and multi-center studies to define preoperatively which patients would benefit from LT.
Objective The aim of this study was to assess the levels of serum lipid and awareness, treatment, and control of dyslipidemia in type 2 diabetes mellitus (T2DM) patients from top-ranked endocrinology ...clinics in large cities of China. Materials and Methods A cross-sectional study in a representative sample of 4807 Chinese adults 40 to 75 years of age was conducted during 2010 to 2011 at 20 endocrinology clinics in top-ranked hospitals covering most of the major cities of China. Serum lipid levels were measured, and treatment of dyslipidemia was recorded and assessed. Results In the present study, the prevalence of dyslipidemia was 67.1% in T2DM subjects. Among those with dyslipidemia, the proportion of awareness and treatment was 68.7% and 55.9%. Among participants with lipid-lowering therapy, 686 subjects achieved the low-density lipoprotein cholesterol (LDL-C) control less than 2.60 mmol/L, with the rate being 39.4%. In those patients with previous cardiovascular disease, the percentage of participants who achieved LDL-C goal (1.80 mmol/L) was 15.3%. Conclusion The prevalence of dyslipidemia is high, and the awareness, treatment, and control of dyslipidemia are relatively low in Chinese T2DM patients. This calls for the awareness and intervention of dyslipidemia in these patients.
Abstract Background Higher intakes of cruciferous vegetables or their constituents have been shown to lower inflammation in animal studies. However, evidence for this anti-inflammatory effect of ...cruciferous vegetable consumption in humans is scarce. Objective/Design In this cross-sectional analysis, we evaluated associations of vegetable intake with a panel of inflammatory and oxidative stress markers among 1,005 middle-aged Chinese women. Dietary intake of foods was assessed by a food frequency questionnaire. Results Multivariable-adjusted circulating concentrations of tumor necrosis factor-α (TNF-α), interlukin-1β (IL-1β), and IL-6 were lower among women with higher intakes of cruciferous vegetables. The differences in concentrations of inflammatory biomarkers between extreme quintiles of cruciferous vegetable intake were 12.66% for TNF-α ( Ptrend =0.01), 18.18% for IL-1β ( Ptrend =0.02), and 24.68% for IL-6 ( Ptrend =0.02). A similar, but less apparent, inverse association was found for intakes of all vegetables combined but not for noncruciferous vegetables. Levels of the urinary oxidative stress markers F2 -isoprostanes and their major metabolite, 2,3-dinor-5,6-dihydro-15-F2t -IsoP, were not associated with intakes of cruciferous vegetables or all vegetables combined. Conclusions This study suggests that the previously observed health benefits of cruciferous vegetable consumption may be partly associated with the anti-inflammatory effects of these vegetables.
Background In a previous study of Chinese patients with idiopathic pulmonary arterial hypertension (IPAH) in the nontargeted therapy era (defined as the time before 2006 when new pulmonary arterial ...hypertension-specific drugs were not available in China), we reported 1- and 3-year survival estimates of only 68% and 39%, respectively. However, it is not yet known whether the survival of patients with pulmonary arterial hypertension is improved in the modern treatment era (defined in China as after 2006). Methods A retrospective cohort study was undertaken in 276 consecutive patients with newly diagnosed incident IPAH and connective tissue disease-related pulmonary arterial hypertension (CTDPAH) who were referred between 2007 and 2009. Baseline characteristics and survival rates in the two groups were compared. Results The 1- and 3-year survival estimates were 92.1% and 75.1%, respectively, in patients with IPAH, and 85.4% and 53.6%, respectively, in patients with CTDPAH. Patients with CTDPAH had a significantly lower mean pulmonary artery pressure, more pericardial effusion, and more severe impairment of the diffusion capacity of the lung for carbon monoxide than patients with IPAH. A diagnosis of CTDPAH, World Health Organization functional class III or IV, single-breath diffusion capacity of the lung for carbon monoxide < 80% predicted, and the presence of pericardial effusion were independent predictors of mortality. The 1- and 3-year survival rates of male patients were 93.5% and 77.5%, respectively, in those with IPAH, and 71.1% and 47.4%, respectively, in those with CTDPAH. Conclusions The survival rates of patients with pulmonary arterial hypertension have improved in China in the modern treatment era, despite the high costs of treatment and financial constraints. However, the survival rates of patients with CTDPAH are inferior to those of patients with IPAH. Our study also indicates poorer survival rates in male patients with CTDPAH.
Summary Invasive mammary carcinoma with neuroendocrine differentiation has been controversial in terms of its definition and clinical outcome. In 2003, the World Health Organization histologic ...classification of tumors designated this entity as neuroendocrine carcinoma of the breast and defined mammary neuroendocrine carcinoma as expression of neuroendocrine markers in more than 50% of tumor cells. It is an uncommon neoplasm. Our recent study showed that it is a unique clinicopathologic entity and has a poor clinical outcome compared with invasive mammary carcinoma with similar pathologic stage. Other investigators have also demonstrated a different molecular profile in this type of tumor from that of invasive ductal carcinoma. It is unknown whether the current prognostic markers for invasive mammary carcinoma are also applicable for neuroendocrine carcinoma of the breast. In the current study, we reviewed the clinicopathologic features and outcome data in 74 cases of mammary neuroendocrine carcinoma from the surgical pathology files at The University of Texas, MD Anderson Cancer Center, to identify relevant prognostic markers for this tumor type. As shown previously by univariate analysis, large tumor size, high nuclear grade, and presence of regional lymph node metastasis are adverse prognostic factors for overall survival and distant recurrence–free survival. In the current study, multivariate analysis revealed that overall survival was predicted by tumor size, lymph node status, and proliferation rate as judged by Ki-67 immunohistochemistry. Only nodal status proved to be a significant independent prognostic factor for distant recurrence–free survival. Neither mitosis score nor histologic grade predicted survival in mammary neuroendocrine carcinoma. Our data suggest that routine evaluation of Ki-67 proliferation index in these unusual tumors may provide more valuable information than mitotic count alone.
Objectives The elephant trunk method was introduced to treat aortic disease. There are a variety of modified elephant trunk methods, including the stented elephant trunk. We retrospectively reviewed ...our experience and evaluated the effectiveness of surgical treatment for acute aortic dissection using the Chinese CRONUS stented elephant trunk technique. Methods From August 2005 to December 2012, 252 patients with acute aortic dissection underwent surgical treatment using the Chinese CRONUS stented elephant trunk technique at the Renmin Hospital of Wuhan University. We review the characteristics of the patients, the surgical method, and the prognosis. Furthermore, we modified the stented elephant trunk technique to simplify the surgical procedure using stented elephant trunk fenestration in 81 patients. Results The procedure was technically successful in all patients. The mean duration of cardiopulmonary bypass, myocardial ischemia, and circulatory arrest was 158 ± 34 minutes, 98 ± 24 minutes, and 27 ± 9 minutes, respectively. The mean stay in the intensive care unit was 74 ± 11 hours. The in-hospital mortality rate was 3.2% (8/252). A 92.2% (225/244) follow-up rate was achieved. Five patients died during follow-up. The diameter of the descending aorta significantly decreased in 173 patients (78.6%), did not change 39 patients (17.7%), and dilated in 8 patients (3.7%). Conclusions In surgery for acute aortic dissection, the Chinese CRONUS stented elephant trunk technique had a low prevalence of morbidity and mortality in our patients. The satisfactory effects demonstrated that the technique is safe and effective in closing the residual false lumen of the descending aorta. Stented elephant trunk fenestration could further simplify the surgical procedure with minimal invasion.
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