Summary Background MicroRNAs (miRNAs) can be used as prognostic biomarkers in many types of cancer. We aimed to identify miRNAs that were prognostic in patients with nasopharyngeal carcinoma. Methods ...We retrospectively analysed miRNA expression profiles in 312 paraffin-embedded specimens of nasopharyngeal carcinoma from Sun Yat-sen University Cancer Center (Guangzhou, China) and 18 specimens of non-cancer nasopharyngitis. Using an 873 probe microarray, we assessed associations between miRNA signatures and clinical outcome in a randomly selected 156 samples (training set) and validated findings in the remaining 156 samples (internal validation set). We confirmed the miRNAs signature using quantitative RT-PCR analysis in 156 samples from a second randomisation of the 312 samples, and validated the miRNA signature in 153 samples from the West China Hospital of Sichuan University in Chengdu, China (independent set). We used the Kaplan-Meier method and log-rank tests to estimate correlations of the miRNA signature with disease-free survival (DFS), distant metastasis-free survival (DMFS), and overall survival. Findings 41 miRNAs were differentially expressed between nasopharyngeal carcinoma and non-cancer nasopharyngitis tissues. A signature of five miRNAs, each significantly associated with DFS, was identified in the training set. We calculated a risk score from the signature and classified patients as high risk or low risk. Compared with patients with low-risk scores, patients with high risk scores in the training set had shorter DFS (hazard ratio HR 2·73, 95% CI 1·46–5·11; p=0·0019), DMFS (3·48, 1·57–7·75; p=0·0020), and overall survival (2·48, 1·24–4·96; p=0·010). We noted equivalent findings in the internal validation set for DFS (2·47, 1·32–4·61; p=0·0052), DMFS (2·28, 1·09–4·80; p=0·030), and overall survival (2·87, 1·38–5·96; p=0·0051) and in the independent set for DFS (3·16, 1·65–6·04; p=0·0011), DMFS (2·39, 1·05–5·42; p=0·037), and overall survival (3·07, 1·34–7·01; p=0·0082). The five-miRNA signature was an independent prognostic factor. A combination of this signature and TNM stage had better prognostic value than did TNM stage alone in the training set (area under receiver operating characteristics 0·68 95% CI 0·60–0·76 vs 0·60 0·52–0·67; p=0·013), the internal validation set (0·70 0·61–0·78 vs 0·61 0·54–0·68; p=0·012), and the independent set (0·70 0·62–0·78 vs 0·63 0·56–0·69; p=0·032). Interpretation Identification of patients with the five-miRNA signature might add prognostic value to the TNM staging system and inform treatment decisions for patients at high risk of progression. Funding Science Foundation of Chinese Ministry of Health, National Natural Science Foundation of China, Pearl River Scholar Funded Scheme, Guangdong Key Scientific and Technological Innovation Program, Guangdong Natural Science Foundation, Fundamental Research Funds for the Central Universities.
To propose a lymph node (N) staging system for nasopharyngeal carcinoma (NPC) based on the International Consensus Guidelines for lymph node (LN) levels and MRI-determined nodal variables.
The MRI ...scans and medical records of 749 NPC patients receiving intensity modulated radiation therapy with or without chemotherapy were retrospectively reviewed. The prognostic significance of nodal level, laterality, maximal axial diameter, extracapsular spread, necrosis, and Union for International Cancer Control/American Joint Committee on Cancer (UICC/AJCC) size criteria were analyzed.
Nodal level and laterality were the only independent prognostic factors for distant failure and disease failure in multivariate analysis. Compared with unilateral levels Ib, II, III, and/or Va involvement (hazard ratio HR 1), retropharyngeal lymph node involvement alone had a similar prognostic value (HR 0.71; 95% confidence interval CI 0.43-1.17; P=.17), whereas bilateral levels Ib, II, III, and/or Va involvement (HR 1.65; 95% CI 1.06-2.58; P=.03) and levels IV, Vb, and/or supraclavicular fossa involvement (HR 3.47; 95% CI 1.92-6.29; P<.01) both significantly increased the HR for distant failure. Thus we propose that the N category criteria could be revised as follows: N0, no regional LN metastasis; N1, retropharyngeal lymph node involvement, and/or unilateral levels Ib, II, III, and/or Va involvement; N2, bilateral levels Ib, II, III, and/or Va involvement; N3, levels IV, Vb, and/or supraclavicular fossa involvement. Compared with the 7th edition of the UICC/AJCC criteria, the proposed N staging system provides a more satisfactory distinction between the HRs for regional failure, distant failure, and disease failure in each N category.
The proposed N staging system defined by the International Consensus Guidelines and laterality is predictive and practical. However, because of no measurements of the maximal nodal diameter on MRI slices, the prognostic significance of LN size needs further evaluation.
A direct comparison of the efficacy and safety profiles of left atrial appendage occlusion (LAAO) devices and novel oral anticoagulants (NOACs) for stroke prevention in atrial fibrillation is ...warranted but currently unavailable.
The aim of this study was to compare the >1-year efficacy and safety of LAAO devices and NOACs for stroke prevention in patients with atrial fibrillation.
We performed a systematic review on randomized controlled trials (RCTs) and observational studies. RCTs were analyzed by means of a network meta-analysis method using warfarin as a bridge to compare LAAO to individual NOAC or all NOACs as a whole. Observational studies were analyzed with the meta-proportion function where pooled event rates were compared.
A total of 6 RCTs and 27 observational studies were included. A network meta-analysis of RCTs indicated that LAAO was less effective than NOACs for stroke prevention (odds ratio 0.86), but had a lower rate of hemorrhagic events during follow-up. However, a meta-proportion analysis of observational studies revealed that LAAO devices were associated with a lower rate of both thromboembolic events (1.8 events per 100 patient-years vs 2.4 events per 100 patient-years) and major bleeding events during follow-up (2.2 events per 100 patient-years vs 2.5 events per 100 patient-years) as compared with NOACs. With prolonged follow-up duration after LAAO implantation, the rate of thromboembolic events decreased (2.1, 1.8, and 1.0 events per 100 person-years for 1, 1-2, and >2 years, respectively).
Although superiority of LAAO over NOACs was not demonstrated by RCTs in terms of stroke prevention, LAAO was found to be consistently associated with a lower rate of both thromboembolic and hemorrhagic events as compared with NOACs in observational studies.
Objective Intrathecal administration of bone marrow stromal cells has been found to produce beneficial effects on ischemia-reperfusion injury to the spinal cord. The blood-spinal cord barrier is ...critical to maintain spinal cord homeostasis and neurologic function. However, the effects of bone marrow stromal cells on the blood-spinal cord barrier after spinal cord ischemia-reperfusion injury are not well understood. This study investigated the effects and possible mechanisms of bone marrow stromal cells on blood-spinal cord barrier disruption induced by spinal cord ischemia-reperfusion injury. Methods This was a prospective animal study conducted at the Central Laboratory of the First Affiliated Hospital, China Medical University. The study used 81 Japanese white rabbits (weight, 1.8-2.6 kg). Spinal cord ischemia-reperfusion injury was induced in rabbits by infrarenal aortic occlusion for 30 minutes. Two days before the injury was induced, bone marrow stromal cells (1 × 108 in 0.2-mL phosphate-buffered saline) were transplanted by intrathecal injection. Hind-limb motor function was assessed using Tarlov criteria, and motor neurons in the ventral gray matter were counted by histologic examination. The permeability of the blood-spinal cord barrier was examined using Evans blue (EB) and lanthanum nitrate as vascular tracers. The expression and localization of tight junction protein occludin were assessed by Western blot, real-time polymerase chain reaction, and immunofluorescence analysis. Matrix metalloproteinase-9 (MMP-9) and tumor necrosis factor-α (TNF-α) expression were also measured. Results Intrathecal transplantation of bone marrow stromal cells minimized the neuromotor dysfunction and histopathologic deficits ( P < .01) and attenuated EB extravasation at 4 hours (5.41 ± 0.40 vs 7.94 ± 0.36 μg/g; P < .01) and 24 hours (9.03 ± 0.44 vs 15.77 ± 0.89 μg/g; P < .01) after spinal cord ischemia-reperfusion injury. In addition, bone marrow stromal cells treatment suppressed spinal cord ischemia-reperfusion injury-induced decreases in occludin ( P < .01). Finally, bone marrow stromal cells reduced the excessive expression of MMP-9 and TNF-α ( P < .01). Conclusions Pre-emptive intrathecal transplantation of bone marrow stromal cells stabilized the blood-spinal cord barrier integrity after spinal cord ischemia-reperfusion injury in a rabbit model of transient aortic occlusion. This beneficial effect was partly mediated by inhibition of MMP-9 and TNF-α and represents a potential therapeutic approach to mitigating spinal cord injury after aortic occlusion.
Background Both percutaneous and perventricular device closures of perimembranous ventricular septal defects (PmVSDs) have drawbacks. This study evaluates the feasibility, safety, and efficacy of ...peratrial device closure of a PmVSD using a probe-assisted delivery system. Methods Seventy-three patients (peratrial group) were enrolled in this study. A 1.5- to 2.0-cm parasternal incision was made in the fourth right interspaces. A Z-shaped malleable hollow probe was inserted into the right atrium. Under transesophageal echocardiographic guidance, it was advanced through the tricuspid valve into the right ventricle. The tip of the probe was adjusted to point to or cross the defect. A flexible guidewire was sent to the left ventricle through the probe to establish a delivery pathway. Then the device was delivered and deployed. Seventy matched control patients, who underwent perventricular device closure of PmVSDs, were identified and assigned to the perventricular group. Results Successful device placement was achieved in 70 of 73 (96%) patients in the peratrial group. The minimal PmVSD diameter ranged from 2.0 to 7.0 mm (median, 3.0 mm). Although the intracardiac manipulation time was longer in the peratrial group, the procedural time and postoperative hospital stays were shorter than in the perventricular group (all p < 0.01). During the follow-up period of 6 to 24 months, no significant device-related complication was found in either group. Conclusions The peratrial device closure of PmVSDs is feasible, safe, and efficacious. Compared with the perventricular technique, it has the advantages of less trauma, shorter hospital stays and procedure time, and better cosmetic results.
Abstract Background Microvascular invasion (MVI) is an important risk factor for survival of patients with hepatocellular carcinoma (HCC) after hepatectomy. However, its impact on patients with ...recurrent HCC who receive a second hepatectomy is unknown. Methods We enrolled 167 patients with HCC who underwent a second hepatectomy because of intrahepatic recurrences. We compared the patients' demographic, tumor, and pathologic characteristics with 766 cases of original hepatectomy. We analyzed the possible risk factors for survival after the first and second hepatectomies and the influence of different MVI patterns on patients' survival after the second hepatectomy. Results The median overall survival was comparable between the first and second hepatectomy groups, 34 (3–84) mo versus 27 (3–57) mo, P = 0.09. For patients who underwent a first hepatectomy, the presence of macro-VI or MVI, an early recurrence pattern, and a total tumor diameter >5 cm were independent risk factors. For survival after the second hepatectomy, MVI patterns that were positive–positive or negative–positive and a total recurrent tumor diameter >5 cm were significant risk factors for survival. Conclusions A second hepatectomy provides satisfying survival for patients with intrahepatic recurrence of HCC after the initial operation. Different MVI patterns affect survival after the second hepatectomy. Because MVI represents the biological behavior of HCC, we place a high premium on the clinical value of MVI after each hepatectomy.
Purpose Postoperative parotid fistula can occur after partial parotidectomy, which is a routine surgical procedure during neck dissection of oral cancers arising from or close to the oropharyngeal ...area. The aim of this study was to evaluate the reliability of vascularized fascia lata for the prevention of postoperative parotid fistula after neck dissection. Materials and Methods A retrospective review was conducted of patients with oral cancer who underwent ablative resection involving the parotid tail and reconstruction using the anterolateral thigh (ALT) flap with a vascularized fascia lata paddle. The vascularized fascia lata paddle was used to seal off the parotid stump by tightly suturing the edges of the fascia lata and parotid wound together. Results Twenty-three patients (18 men and 5 women) with primary oral cancer arising from or close to the oropharyngeal area were enrolled. The mean area of parotid defect was 16.7 cm2 and the mean area of fascia lata harvested was 21.8 cm2 . All flaps survived. Pressure dressing or anticholinergic drugs were not used in any case. During the follow-up period, there was no clinical evidence of the development of parotid fistula. Conclusion The vascularized fascia lata paddle is a reliable option for the prevention of postoperative parotid fistula after neck dissection of oral cancer.
Abstract Background Rheumatoid arthritis (RA) is associated with an increased incidence of atrial fibrillation (AF). This study evaluated the safety and efficacy of catheter ablation (CA) in the ...treatment of AF in patients with RA, which has not been previously reported. Methods A total of 15 RA patients with AF who underwent CA were enrolled. For each RA patient, we selected 4 individuals (control group, 60 patients in total) who presented for AF ablation in the absence of structural heart or systemic disease and matched the RA patients with same gender, age (±2 years), type of AF, and procedure date. Results Patients with RA had a significantly higher C-reactive protein level (1.81 ± 2.35 mg/dl vs. 4.14 ± 2.30 mg/dl, p = 0.0320), white blood cell count (5632 ± 1200 mm3 vs. 6361 ± 1567 mm3 , p = 0.0482), and neutrophil count (3308 ± 973 mm3 vs. 3949 ± 1461 mm3 , p = 0.0441). At 2-year follow-up, atrial tachyarrhythmia (ATa) recurrence rate in the RA group (33.3%, 5/15) was similar to that in the control group (31.7%, 19/60; p = 0.579) after single procedure. In all the five patients from the RA group who developed recurrence, ATa relapsed within 90 days following index procedure (median recurrence time 18 days vs. 92 days in control group; p = 0.0373). Multivariate Cox regression analysis showed that hypertension and left atrial diameter but not RA, C-reactive protein, white blood cell count, and neutrophil count were independent predictors of ATa recurrence. Conclusions Catheter ablation of AF can be safely performed in patients with RA, with a success rate comparable to that of patients without RA. RA patients tend to develop early ATa recurrence after AF ablation.
Improved markers for predicting recurrence are needed to stratify patients with localised (stage I–III) renal cell carcinoma after surgery for selection of adjuvant therapy. We developed a novel ...assay integrating three modalities—clinical, genomic, and histopathological—to improve the predictive accuracy for localised renal cell carcinoma recurrence.
In this retrospective analysis and validation study, we developed a histopathological whole-slide image (WSI)-based score using deep learning allied to digital scanning of conventional haematoxylin and eosin-stained tumour tissue sections, to predict tumour recurrence in a development dataset of 651 patients with distinctly good or poor disease outcome. The six single nucleotide polymorphism-based score, which was detected in paraffin-embedded tumour tissue samples, and the Leibovich score, which was established using clinicopathological risk factors, were combined with the WSI-based score to construct a multimodal recurrence score in the training dataset of 1125 patients. The multimodal recurrence score was validated in 1625 patients from the independent validation dataset and 418 patients from The Cancer Genome Atlas set. The primary outcome measured was the recurrence-free interval (RFI).
The multimodal recurrence score had significantly higher predictive accuracy than the three single-modal scores and clinicopathological risk factors, and it precisely predicted the RFI of patients in the training and two validation datasets (areas under the curve at 5 years: 0·825–0·876 vs 0·608–0·793; p<0·05). The RFI of patients with low stage or grade is usually better than that of patients with high stage or grade; however, the RFI in the multimodal recurrence score-defined high-risk stage I and II group was shorter than in the low-risk stage III group (hazard ratio HR 4·57, 95% CI 2·49–8·40; p<0·0001), and the RFI of the high-risk grade 1 and 2 group was shorter than in the low-risk grade 3 and 4 group (HR 4·58, 3·19–6·59; p<0·0001).
Our multimodal recurrence score is a practical and reliable predictor that can add value to the current staging system for predicting localised renal cell carcinoma recurrence after surgery, and this combined approach more precisely informs treatment decisions about adjuvant therapy.
National Natural Science Foundation of China, and National Key Research and Development Program of China.
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