Surgical site infection after posterior lumbar interbody fusion and instrumentation in patients with lumbar degenerative disease.

We designed this retrospective study with aims to investigate the incidence and risk factors associated with surgical site infection (SSI) following posterior lumbar interbody fusion (PLIF) and instrumentation in patients with lumbar degenerative disease. Eligible patients treated between January 2016 and June 2019 were included. Electronic medical records were inquired for data extraction and collection. Patients with SSI and without SSI were compared using the univariate analyses, and the association between variables and risk of SSI was investigated using multivariate logistics regression analyses. Among 1269 patients, 43 were found to have SSI, indicating a rate of 3.4%. Microbiological culture tests showed 88.4% patients had a positive result. Four SSIs were caused by mixed bacterial, and the remaining 34 by single bacteria. Multiple drug-resistant strains were detected in 25 (65.8%) SSIs, with meticillin-resistant coagulase-negative staphylococcus (MRCNS) predominating (12, 48.0%). ASA III and above (odd ratio (OR), 1.67; 95% confidence interval (CI), 1.11 to 3.07), preoperative stay (OR, 1.13; 95% CI, 1.04 to 1.23), heart disease (OR, 2.88; 95% CI, 1.24 to 6.71), diabetes mellitus (OR, 3.28; 95% CI, 1.66 to 6.47) and renal insufficiency (OR, 4.23; 95% CI, 1.26 to 10.21), prolonged prophylactic antibiotics use (OR, 4.43; 95% CI, 2.30 to 8.54), and the reduced lymphocyte count (OR, 2.11; 95% CI, 1.03 to 4.33) were identified as independent risk factors associated with SSI. These factors, although most not modifiable, should be kept in mind, optimised for surgical conditions, or readily adjusted in the future postoperative management of antibiotics, to reduce postoperative SSIs.

Risk factors of postoperative deep vein thrombosis (DVT) under low molecular weight heparin (LMWH) prophylaxis in patients with thoracolumbar fractures caused by high-energy injuries.

To determine the incidence of DVT and to evaluate the risk factors of DVT under LMWH prophylaxis in patients with thoracolumbar fractures caused by high­energy injuries postoperatively. A total of 534 patients from January 2016 to November 2019 were included in this retrospective study. Medical record data, including demographic data, perioperative variables, and laboratory results, were collected. LMWH prophylaxis was used for DVT in all the patients. The incidence and risk factors of DVT after surgery were identified by logistic regression analysis and receiver operating characteristic (ROC) curve analysis. The overall incidence of postoperative DVT was 18.91% (101/534). Three patients (0.56%) had proximal DVT and ninety-eight (18.35%) patients had distal DVT. The incidence of postoperative DVT in patients with thoracic fractures was 26.80% and 15.50% with lumbar fractures. The multivariate analysis showed that six risk factors increased the incidence of postoperative DVT, including advanced age, decreased lower extremity motor, blood transfusion, duration of bed rests, fibrinogen (FIB), and D-dimer. The ROC analysis indicated that the diagnostic value of D-dimer was highest whose area under the ROC curves (AUC) value was 0.754. Despite LMWH prophylaxis, the risk of postoperative DVT is still very high, especially in thoracic fracture. Advanced age, decreased lower extremity motor, blood transfusion, duration of bed rests, FIB, and D-dimer are risk factors for DVT. Moreover, the diagnostic value of D-dimer is the highest among these factors.

Incidence and predictors of surgical site infection after ORIF in calcaneus fractures, a retrospective cohort study.

BACKGROUND: Occurrence of calcaneus fractures is on the up trend. Owing to its unique anatomical morphology and limited soft-tissue envelope, management of calcaneus fractures is a challenge to the orthopaedic surgeon, and surgical site infection (SSI) is one of the serious postoperative complications. In order to decrease the incidence of wound breakdown and improve clinical outcomes, it is necessary to understand which factors were associated with SSI. The aim of this study was to identify predictors of SSI and quantify the incidence of SSI in calcaneus fractures following open reduction and internal fixation (ORIF). METHODS: This retrospective study was performed at a level 1 trauma center from January 2014 to June in 2017. Data of adult patients with calcaneus fractures treated by ORIF were extracted from the electronic medical records. A total of 681 patients were collected. We reviewed the patients' demographics, characteristics of fracture, treatment-related variables, and indexes of laboratory examination. Univariate and multivariate logistic analysis models were performed respectively to determine independent predictors of SSI. RESULTS: Sixty-six patients developed SSI in this study. The overall incidence of SSI after ORIF of calcaneus fracture was 9.7%, with 2.9% for deep infection and 6.8% for superficial SSI. Independent predictors of SSI identified by multivariate analysis were open fracture (odds ratio = 9.48, 95% CI = 4.53-19.85, P = 0.00007), high-energy injury (odds ratio = 2.07, 95% CI = 1.16-3.70, P = 0.01437), ASA class 3 or higher (odds ratio = 3.50, 95% CI = 1.18-10.37, P = 0.02401), and intraoperative temperature < 36.0 °C (odds ratio = 1.69, 95% CI = 1.13-2.28, P = 0.04410). CONCLUSION: The SSI incidence was high (9.7%) for calcaneus fractures following ORIF. External fixation plays an important role in the treatment of severely displaced and depressed intra-articular or open calcaneus fractures. Increased ASA class and intraoperative hypothermia were associated with wound breakdown, and elaborative evaluation of fracture and soft-tissue damage was vitally necessary in this at-risk population.

A dosimetric comparison of double-arc volumetric arc therapy, step-shoot intensity modulated radiotherapy and 3D-CRT for left-sided breast cancer radiotherapy after breast-conserving surgery.

OBJECTIVE: To compare the dosimetric and efficiency differences for left-sided breast cancer radiotherapy after breast-conserving surgery among three different planning techniques: double-arc volumetric-modulate arc therapy (VMAT), step-shoot intensity-modulated radiotherapy (sIMRT) and three-dimensional conformal radiation therapy (3D-CRT). MATERIALS AND METHODS: A total of 17 female patients with left-sided breast cancer who underwent breast-conserving surgery were selected; the prescription doses were 50 Gy in 25 fractions. For every patient VMAT, sIMRT and 3D-CRT plans were generated within the Monaco treatment planning system for an Axesse™ accelerator equipped with the Agility MLC. The Conformity Index (CI), the Homogeneity Index (HI), the dose volume histogram (DVH) parameters for the organs at risk and the delivery efficiency were evaluated. RESULTS: The VMAT plans showed on average higher CI of PTV (0.77 ± 0.03) than both sIMRT (0.68 ± 0.02) and 3D-CRT (0.55 ± 0.04) plans (P< 0.05). The HI values in the VMAT, sIMRT and 3D-CRT plans were 0.10 ± 0.01 0.09 ± 0.01 and 0.13 ± 0.01 (P> 0.05), respectively, and the differences among the three techniques were not statistically significant. In the ipsilateral lung, the VMAT plans showed lower Dmean, V30, V20, and V10 than the sIMRT and 3D-CRT (P< 0.05); however, there was no significant difference in V5. In the heart, the VMAT plans had lower V30 and V20 than the sIMRT and 3D-CRT plans (P< 0.05), but there was no significant difference in the Dmean and V5. In the contralateral lung, the VMAT plans showed higher Dmean and V5 than sIMRT and 3D-CRT (P< 0.05). In the contralateral breast, the VMAT plans had a higher V5 than the sIMRT and 3D-CRT plans (P< 0.05). The VMAT plans had higher MU's than sIMRT and 3D-CRT, while the treatment times were lower than that of sIMRT. CONCLUSION: For left-sided breast cancer radiotherapy after breast-conserving surgery, the VMAT plans had a better CI than the sIMRT and 3D-CRT plans. The VMAT and the sIMRT plans had better HI than the 3D-CRT plans, but no significant difference was observed between VMAT and sIMRT.

Systemic immune-inflammation index predicts the clinical outcome in patients with nasopharyngeal carcinoma: a propensity score-matched analysis.

Systemic immune-inflammation index (SII), based on peripheral lymphocyte, neutrophil, and platelet counts, was recently investigated as a prognostic marker in several tumors. However, SII has not been reported in nasopharyngeal carcinoma (NPC). We evaluated the prognostic value of the SII in 327 patients with NPC. Univariate and multivariate analyses were calculated by the Cox proportional hazards regression model. The time-dependent receiver operating characteristics (ROC) curve was used to compare the discrimination ability for OS. PSM (propensity score matching) was carried out to imbalance the baseline characteristics. Our results showed that SII, PLR, NLR and MLR were all associated with OS in NPC patients in the Kaplan-Meier survival analysis. SII (HR: 2.26; 95% CI: 1.40-3.66; P=0.001), NLR (HR: 1.66; 95% CI: 1.08-2.53; P=0.020), and MLR (HR: 1.99; 95% CI: 1.17-3.39; P=0.011) were identified to be the independent prognostic factors. The AUC for SII was bigger than NLR, PLR and MLR for predicting survival in patients with NPC in 3 or 5-years. In the PSM analysis, SII remained an independent predictor for OS in NPC patients (HR=2.08, CI 1.22-3.55, P=0.007). SII is a novel, simple and inexpensive prognostic predictor for patients with NPC. The prognostic value of SII is superior to PLR, NLR and MLR.

The Hippocampus Sparing Volume Modulated Arc Therapy does not Influence Plan Quality on Locally Advanced Nasopharyngeal Carcinoma Patients.

Irradiation on hippocampus would lead to neuro-cognitive dysfunction in locally advanced nasopharyneal carcinoma (LA-NPC) patients accepting radiotherapy. Our study here aimed to investigate if undergoing hippocampus sparing (HS) volume modulated arc therapy (VMAT) would influence the plan quality in LA NPC patients. We designed three kinds of radiotherapeutic plans for 11 LA NPC patients: conventional VMAT (C-VMAT), HS-VMAT and HS intensity modulated radiation therapy with dynamic multileaf collimator (HS-dMLC). And the dose distribution on targets and surrounding organs at risk (OAR) were carefully evaluated. We found out that the expected doses on hippocampus were significantly lowered in HS-VMAT (899 ± 378 cGy) and HS-dMLC (896 ± 321 cGy) as compared to C-VMAT (1518 ± 337 cGy, p < 0.05), but meaningless difference was presented on plan quality of targets (p > 0.05). Moreover, lower radiation doses on brain stem were observed in HS-VMAT plan in comparison with C-VMAT plan (p < 0.05). However, there were no statistically meaningful diversities in the doses received by other OARs among all plans. Here we concluded that HS-VMAT presented promising advantages on protecting hipppcampus and brain stem as compared to C-VMAT and HS-dMLC, but enthusiastically had no effects on plan quality in LA-NPC patients.

Assessment of local treatment modalities for FIGO stage IB-IIB cervical cancer: A propensity-score matched analysis based on SEER database.

The aim of this study was to investigate the impact of local treatment modalities on the survival of patients with International Federation of Gynecology and Obstetrics (FIGO) stage IB-IIB cervical cancer, including cancer-directed surgery (CDS) alone and CDS combined with radiotherapy (RT). A total of 8,357 patients with cervical cancer between 1988 and 2013 were included in the final study cohort, including 4,298 (51.4%) patients who underwent CDS alone and 4,059 (48.6%) patients who received combination therapy. Univariate and multivariate analyses showed that local treatment modalities were prognostic factors for cause-specific survival (CSS). Patients who received combination therapy had worse CSS (HR = 1.38; 95% CI = 1.20-1.59; P < 0.001). Subgroup analyses showed the prognostic effect of local treatment modalities was significantly influenced by FIGO stage. In the propensity-score matched (PSM) dataset, CDS was associated with better CSS (P < 0.001) for patients with IB-IIA cervical cancer; nevertheless, no differences were observed in CSS (P = 0.639) for patients with IIB cervical cancer. In conclusion, radical surgery was the preferred treatment for patients with IB-IIA cervical cancer, and there was no difference between radical surgery alone and combination therapy for patients with IIB cervical cancer.

Evaluating the Prognostic Value of microRNA-203 in Solid Tumors Based on a Meta-Analysis and the Cancer Genome Atlas (TCGA) Datasets.

BACKGROUND: It has been reported that miR-203 expression was aberrant in various types of cancers, and it could be used as a prognostic biomarker. Therefore, in this study, we aimed to evaluate the prognostic value of miR-203 expression in solid tumors by using meta-analysis and The Cancer Genome Atlas (TCGA) datasets. METHODS: By doing a literature research in PubMed, Embase and the Cochrane Library (last update by December 2016), we were able to identify the studies assessing the prognostic role of miR-203 in various tumors. We then used TCGA datasets to validate the results of meta-analysis. RESULTS: 33 studies from 26 articles were qualified and enrolled in this meta-analysis. Pooled analyses showed that higher expression of miR-203 in tissues couldn't predict poor overall survival (OS) and progression-free survival (PFS) in solid tumors. However, the results of subgroup analyses revealed that the upregulation of tissue miR-203 expression was associated with poor OS in colorectal cancer (hazard ratio (HR)=1.81, 95% confidence intervals (CI) 1.31-2.49; P<0.001), pancreatic cancer (HR=1.19, 95% CI 1.09-1.31; P<0.001) and ovarian cancer (HR=1.85, 95% CI 1.45-2.37; P<0.001); but it had opposite association in liver cancer (HR=0.52, 95% CI 0.28-0.97; P=0.040) and esophageal cancer (HR=0.41, 95% CI 0.25-0.66; P<0.001). Based on TCGA datasets, we found the same results for pancreatic cancer and esophageal cancer, but not for colorectal cancer and liver cancer. Moreover, patients with high circulating miR-203 in blood had significantly poor OS and PFS in colorectal cancer and breast cancer. CONCLUSION: Our study showed that the prognostic values of tissue miR-203 varied in different tumor types. In addition, the upregulation of circulating miR-203 in blood was associated with poor prognosis in colorectal cancer and breast cancer.

Assessment of Lymph Node Ratio to Replace the pN Categories System of Classification of the TNM System in Esophageal Squamous Cell Carcinoma.

INTRODUCTION: The seventh edition of the TNM staging system for esophageal cancer outlined by the American Joint Committee on Cancer (AJCC) defines the N classification on the basis of the number of metastatic lymph nodes. However, this classification is dependent on the actual number of examined lymph nodes. Here in this study, we have focused on revising this N classification system with the metastatic lymph nodes ratio (LNR) and also assessing whether this modification to the current AJCC staging system can better define the prognostic characteristics of esophageal squamous cell carcinoma (ESCC). METHODS: We retrospectively reviewed 916 patients with ESCC who underwent curative resection. Prognostic performance of two staging systems was compared using the Akaike information criterion value and receiver operating characteristics curve. In addition, decision curve analysis evaluated the clinical practical usefulness of the prediction models by quantifying their net benefits. RESULTS: The univariate and multivariate Cox regression analyses indicated that LNR was an independent risk factor for overall survival. The modified staging system based on LNR had better discriminatory ability, monotonicity, homogeneity, and stratification than the TNM staging system in determining the prognosis of patients with ESCC. However, the decision curves analysis suggested that the modified staging based on LNR has poor clinical practical value over the AJCC TNM staging system. CONCLUSIONS: LNR can supplement the pN categorization system for more effective evaluation of prognosis. But the modified staging system based on LNR has a poor clinical practical value for patients with ESCC compared with the current TNM system and is not superior to AJCC pN staging for ESCC.

Prognostic role of high B7-H4 expression in patients with solid tumors: a meta-analysis.

BACKGROUND: Recently, many studies have shown that B7-H4 exhibits altered expression in various cancers. We performed a meta-analysis to evaluate the prognostic role of B7-H4 expression in solid tumors. RESULTS: Data from 18 observational studies and 2467 patients were summarized. An elevated baseline B7-H4 was significantly associated with worse OS (pooled HR = 1.79; 95% CI = 1.56-2.06). Differences across subgroups of tumor type, patients' ethnicity, analysis type, HR obtain method and cut-off value were not significant (PD = 0.313, PD = 0.716, PD = 0.896, PD = 0.290 and PD = 0.153, respectively). Furthermore, patients with high B7-H4 had a significantly shorter DFS (pooled HR = 2.12; 95%CI = 1.45-3.09). MATERIALS AND METHODS: We searched PubMed, Embase and the Cochrane Library (last update by November 26, 2015) to identify studies assessing the effect of B7-H4 on survival of cancer patients. Pooled hazard ratios (HRs) for overall survival (OS) and disease-free survival (DFS) were estimated using fixed-effects models and random-effects models respectively. CONCLUSIONS: This meta-analysis clarified that high B7-H4 expression in tissue was significantly associated with poor survival in patients with solid tumors. Future clinical studies are warranted to determine whether B7-H4 blockade has a favorable effect on disease recurrence and mortality.

Dosimetric comparison between step-shoot intensity-modulated radiotherapy and volumetric-modulated arc therapy for upper thoracic and cervical esophageal carcinoma.

To compare and analyze the dosimetric characteristics of volumetric modulated arc therapy (VMAT) vs step-shoot intensity-modulated radiation therapy (sIMRT) for upper thoracic and cervical esophageal carcinoma. Single-arc VMAT (VMAT1), dual-arc VMAT (VMAT2), and 7-field sIMRT plans were designed for 30 patients with upper thoracic or cervical esophageal carcinoma. Planning target volume (PTV) was prescribed to 50.4Gy in 28 fractions, and PTV1 was prescribed to 60Gy in 28 fractions. The parameters evaluated included dose homogeneity and conformality, dose to organs at risk (OARs), and delivery efficiency. (1) In comparison to sIMRT, VMAT provided a systematic improvement in PTV1 coverage. The homogeneity index of VMAT1 was better than that of VMAT2. There were no significant differences among sIMRT, VMAT1, and VMAT2 in PTV coverage. (2) VMAT1 and VMAT2 reduced the maximum dose of spinal cord as compared with sIMRT (p < 0.05). The rest dose-volume characteristics of OARs were similar. (3) Monitor units of VMAT2 and VMAT1 were more than sIMRT. However, the treatment time of VMAT1, VMAT2, and sIMRT was (2.0 ± 0.2), (2.8 ± 0.3), and (9.8 ± 0.8) minutes, respectively. VMAT1 was the fastest, and the difference was statistically significant. In the treatment of upper thoracic and cervical esophageal carcinoma by the AXESSE linac, compared with 7-field sIMRT, VMAT showed better PTV1 coverage and superior spinal cord sparing. Single-arc VMAT had similar target volume coverage and the sparing of OAR to dual-arc VMAT, with shortest treatment time and highest treatment efficiency in the 3 kinds of plans.

Phase II study of computed tomography-guided (125)I-seed implantation plus chemotherapy for locally recurrent rectal cancer.

BACKGROUND AND PURPOSE: This trial evaluated the efficacy and safety of CT guided (125)I-seed implantation (CTII) plus chemotherapy with fluorouracil, leucovorin, and irinotecan (FOLFIRI) compared with FOLFIRI alone as second-line treatment for locally recurrent rectal cancer (LRRC). MATERIAL AND METHODS: Patients with LRRC who received one prior chemotherapy regimen were enrolled and divided randomly assigned to FOLFORI alone (Arm A) and FOLFORI plus CTII (Arm B). The primary endpoint was local control time (LCT). Overall survival (OS) and treatment related adverse events (TRAEs) were also observed. RESULTS: Fifty-seven patients were enrolled from October 2008 and December 2014. Twenty-seven were assigned into Arm A and 30 into Arm B. The overall response rate of locally recurrent tumor was improved to 100% in Arm B versus 29.6% in Arm A (P<0.001). A significant longer LCT was observed in Arm A (P<0.001); median LCT was 12 months in Arm B versus 4 months in Arm A. A borderline significant improvement in OS was also observed in Arm B (P=0.0464); median OS was 25 months in Arm B versus 19 months in Arm A. For patients without distant metastases, median OS was 37 months in Arm B versus 21 months in Arm A (P=0.0101). For patients with (neo)adjuvant radiotherapy (ART), a longer LCT and OS were also found in Arm B (P<0.001 and P=0.0217, respectively). TRAEs were not serious generally. There was no statistically significant difference in treatment related toxicity between Arm A and B both for all patients and patients receiving ART. CONCLUSIONS: CTII plus FOLFIRI improves the LCT with tolerable toxicities as a second-line treatment in patients with local recurrent rectal cancer, and is helpful to prolong the OS, particularly in patients without distant metastases or with a history of radiotherapy.

Analysis of the correlation between P53 and Cox-2 expression and prognosis in esophageal cancer.

The present study aimed to explore the importance of P53 and Cox-2 protein expression in esophageal cancer and assess their influence on prognosis. The expression of P53 and Cox-2 was assessed in esophageal cancer samples from 195 patients subjected to radical surgery at Changzhou First People's Hospital (Changzhou, China) between May 2010 and December 2011. Expression of P53 and Cox-2 proteins were detected in 60.5% (118/195) and 69.7% (136/195) of the samples, respectively, and were co-expressed in 43.1% (84/195) of the samples. A correlation was identified between P53 expression and overall survival (OS) (P=0.0351) as well as disease-free survival (DFS) (P=0.0307). In addition, the co-expression of P53 and Cox-2 also correlated with OS (P=0.0040) and DFS (P=0.0042). P53 expression (P=0.023), TNM staging (P<0.001) and P53/Cox-2 co-expression (P=0.009) were identified as independent factors affecting OS in patients with esophageal cancer via a Cox multivariate regression model analysis. A similar analysis also identified P53 expression (P=0.020), TNM staging (P<0.001) and P53/Cox-2 co-expression (P=0.008) as independent prognostic factors influencing DFS in these patients. Binary logistic regression analysis demonstrated a correlation between P53 expression (P=0.012), TNM staging (P<0.001), tumor differentiation level (P=0.023) and P53/Cox-2 co-expression (P=0.021), and local recurrence or distant esophageal cancer metastasis. The results of the present study indicate that P53 and Cox-2 proteins may act synergistically in the development of esophageal cancer, and the assessment of P53/Cox-2 co-expression status in esophageal cancer biopsies may become an important diagnostic criterion to evaluate the prognosis of patients with esophageal cancer.

Prognostic nomogram integrated systemic inflammation score for patients with esophageal squamous cell carcinoma undergoing radical esophagectomy.

Growing evidence indicates that nomogram combined with the biomarkers of systemic inflammation response could provide more accurate prediction than conventional staging systems in tumors. This study aimed to establish an effective prognostic nomogram for resectable thoracic esophageal squamous cell carcinoma (ESCC) based on the clinicopathological parameters and inflammation-based prognostic scores. We retrospectively investigated 916 ESCC patients who underwent radical esophagectomy. The predictive accuracy and discriminative ability of the nomogram were determined by concordance index (C-index) and calibration curve, and compared with the 6(th) and 7(th) AJCC TNM classifications. The neutrophil lymphocyte ratio (NLR), C-reactive protein albumin (CRP/Alb) ratio, histological grade, T stage and modified N stage were integrated in the nomogram. The C-index of the nomogram for predicting the survival was 0.72, which showed better predictive ability of OS than the 6(th) or 7(th) TNM stages in the primary cohort (P < 0.001). The calibration curve showed high consistency between the nomogram and actual observation. The decision curve analysis showed more potential of clinical application of the prediction models compared with TNM staging system. Moreover, our findings were supported by the validation cohort. The proposed nomogram showed more accurate prognostic prediction for patients with ESCC after radical esophagectomy.

Collimator rotation in volumetric modulated arc therapy for craniospinal irradiation and the dose distribution in the beam junction region.

PURPOSE: The purpose of this study was to investigate the role of beam collimator rotation in Volumetric Modulated Arc Therapy (VMAT) for craniospinal irradiation (CSI), and the impact on dose distribution in the beam junctions. METHODS: Six adult patients were selected for the study. Six VMAT plans with different collimator angles were generated for each patient. The patients were treated in supine position with two beam isocenters. The plans were evaluated by analysis of Dose-Volume Histogram (DVHs) data for planning target volume (PTV) and organs at risk (OAR), and conformity index (CI) and homogeneity index (HI) for the target. Dose distributions in the beam junctions were examined carefully and experimentally validated in phantom, with measurement using an ion chamber array and film. RESULTS: The mean values of HI and CI for the plans with different beam collimator angles were not significantly different. The numbers of segments, monitor units (MUs) and the delivery time of the plans with 45° beam collimator were obviously higher than those in plans with other beam collimator angles. When collimator angle for both sets of beams were set at 0°, there was a 1 mm low dose gap measured in the junction region. CONCLUSIONS: By setting the collimator angle to 45°, only two isocenters were needed for the treatment of a target with the length up to 90 cm. The HI and CI of the plans were almost the same, regardless if the collimator angles were at 0°. The collimator angles for at least one set of beams should be off 0° in order to avoid a dose gap in the beam junction region.

The status of perineural invasion predicts the outcomes of postoperative radiotherapy in locally advanced esophageal squamous cell carcinoma.

BACKGROUND: Prognosis of locally advanced esophageal squamous cell carcinoma (ESCC) remains dismal even after curative resection and adjuvant radiotherapy. New biomarkers for predicting prognosis and treatment outcomes are needed for improved treatment stratification of patients with locally advanced ESCC. The prognostic and treatment predictive significance of perineural invasion (PNI) in the locally advanced ESCC remains unclear. This study aimed to examine the effect of PNI on the outcomes of locally advanced ESCC patients after curative resection with or without postoperative radiotherapy (PORT). PATIENTS AND METHODS: We retrospectively reviewed 262 consecutive locally advanced ESCC patients who underwent curative resection. Tumors sections were re-evaluated for PNI by an independent pathologist blinded to the patients' outcomes. Overall survival (OS) and disease-free survival (DFS) were determined using the Kaplan-Meier method; univariate log-rank test and multivariate Cox proportional hazard model were used to evaluate the prognostic value of PNI. RESULTS: Finally, 243 patients were analyzed and enrolled into this study, of which 132 received PORT. PNI was identified in 22.2% (54/243) of the pathologic sections. The 5-year DFS was favorable for PNI-negative patients versus PNI-positive patients (21.3% vs. 36.7%, respectively; P = 0.005). The 5-year OS was 40.3% for PNI-negative patients versus 21.7% for PNI-positive patients (P < 0.001). On multivariate analysis, PNI was an independent prognostic factor. In a subset analysis for patients received PORT, PNI was evaluated as a prognostic predictor as well (P < 0.05). In contrast to patients without PORT, PORT couldn't improve the disease recurrence and survival in locally advanced ESCC patients with PNI-positive (P > 0.05). CONCLUSIONS: PNI could serve as an independent prognostic factor and prognosticate treatment outcomes in locally advanced ESCC patients. The PNI status should be considered when stratifying high-risk locally advanced ESCC patients for adjuvant radiotherapy. Future prospective study is warranted to confirm our results.

Proposed Modification of Nodal Staging as an Alternative to the Seventh Edition of the American Joint Committee on Cancer Tumor-Node-Metastasis Staging System Improves the Prognostic Prediction in the Resected Esophageal Squamous-Cell Carcinoma.

INTRODUCTION: The 7th American Joint Committee on Cancer (AJCC) tumor-node-metastasis staging system for esophageal cancer defined N classification based on the number of metastatic lymph nodes (LNs). However, this classification might neglect the extent of LNs metastasis. This study aimed to revise N classification based on the extent of LNs metastasis and propose a modification to the current AJCC staging system for better representing the prognostic characteristics of Chinese esophageal squamous-cell carcinoma (ESCC). METHODS: We retrospectively reviewed 1993 ESCC patients who underwent curative resection. The proposed N categories based on the number of LNs metastasis stations were compared with the current staging system by univariate and multivariate Cox regression analyses. Homogeneity, discriminatory ability, and monotonicity of gradients of two staging systems were compared using likelihood ratio χ statistics and Akaike information criterion calculations. RESULTS: The survival differences were not significant for N2 versus N3 category (p = 0.231) and stages IIIB versus IIIC (p = 0.713) based on the 7th AJCC staging system. When the modified staging system was adopted, the survival difference for N2 versus N3 and IIIB versus IIIC could be well discriminated. Statistical analysis showed that the modified staging system had higher likelihood ratio χ scores and smaller Akaike information criterion values than the 7th AJCC staging system, which represented the optimum prognostic stratification. CONCLUSIONS: The modified staging system with the revised N categories based on the number of LNs metastasis stations better predicts the survival of Chinese ESCC population than the 7th AJCC staging system. Further studies are required to confirm this result.

Directed evolution of a ß-1,3-1,4-glucanase from Bacillus subtilis MA139 for improving thermal stability and other characteristics.

In order to improve some characteristics of a ß-1,3-1,4-glucanase from Bacillus subtilis MA139, directed evolution was conducted in this study. After error-prone PCR, the ß-1,3-1,4-glucanase gene, glu-opt, was cloned into the vector pBGP1 and transformed into Pichia pastoris X-33 to construct a mutant library. Three variants named as 7-32, 7-87, and 7-115 were screened from 8000 colonies. Amino-acid sequence analysis showed that these mutants had one or two amino-acid substitutions (7-32: T113S, 7-87: M44V/N53H, and 7-115: N157D). The variants were over-expressed in P. pastoris by methanol induction. After purification of the enzyme proteins, the characteristics of the variants were analyzed in detail. It indicated that these mutant enzymes had broader ranges of pH value and better pH stability than the wild-type enzyme. The mutant enzyme 7-87 had the best ability to tolerate an acid environment (pH 2.0), while the wild-type enzyme had no activity under this condition. Moreover, all these mutants demonstrated improved thermal stability. In particular, the mutant enzyme 7-32 had residual enzymatic activity of 60% and 40% after being incubated at 80 °C and 90 °C for 10 min. While, the wild-type enzyme had no residual enzymatic activity after being incubated at 80 °C for 4 min. In addition, the mutant enzymes had better tolerance to some chemicals than the wild-type enzyme. The improved stability could enhance the prospects for this enzyme to have use in the feed industry to reduce the effects of the anti-nutritional factor ß-glucan.

Prognostic role of tissue and circulating microRNA-200c in malignant tumors: a systematic review and meta-analysis.

BACKGROUND: Recently, many studies have shown that microRNAs (miRNA) exhibit altered expression in various cancers and may serve as prognostic biomarkers. We performed a systematic review and meta-analysis to evaluate the prognostic role of miR-200c expression in different cancers. METHODS: Studies were recruited by searching PubMed, Embase and the Cochrane Library (last search update was May 2014) and assessed by further quality evaluation. RESULTS: A total of 25 studies dealing with various carcinomas were identified for systematic review. Among them, 18 studies were ultimately included in the meta-analysis. Our results indicated that the expression of tissue miR-200c was not associated with OS and PFS in various carcinomas; however, downregulation of tissue miR-200c did predict poor OS of patients with stage I disease (HR=0.41, 95% CI 0.25-0.68, P=0.001). Furthermore, overexpression of blood miR-200c was significantly related to poor OS and PFS (HR=3.07 95% CI 1.58-5.96 P=0.001, HR=2.26 95% CI 1.66-3.08 P<0.001, respectively), especially in patients with advanced disease. CONCLUSION: This systematic review and meta-analysis clarified that low expression of miR-200c in primary tissue was significantly associated with poor survival in cancer patients at early stage, whereas a high level of blood miR-200c predicted poor prognosis in patients with advanced tumors.