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Necrotizing funisitis is a distinct lesion of the umbilical cord associated with chorioamnionitis and bloodborne fetal infection. The lesion may be a response to microorganisms in Wharton's jelly. A common microorganism detected in chorioamnionitis is Ureaplasma urealyticum (U. urealyticum). This study hypothesizes that U. urealyticum DNA will be present in Wharton's jelly in necrotizing funisitis.Necrotizing funisitis was identified retrospectively from a 2-year pathology database and confirmed in review. Paraffin fixed embedded tissue sections of the lesion were prepared for polymerase chain reaction (PCR) by using primers to identify U. urealyticum. Twenty matched controls without funisitis were similarly processed. Clinical data included serological tests of common bloodborne infections in the mothers and infants, and U. urealyticum PCR results in the urine of the neonates.Fourteen cases of necrotizing funisitis were identified in 7,416 examined placentas. Nine of these umbilical cords were positive by PCR for U. urealyticum (64.3%). Nineteen of twenty control cases were negative. Eight of ten neonates (80%) also had positive urine PCR tests for U. urealyticum. No infants or mothers had evidence of bloodborne fetal infection.U. urealyticum DNA was present in Wharton's jelly by PCR testing in the majority of the necrotizing funisitis lesions tested. This result supports a possible causative role for U. urealyticum in many cases of necrotizing funisitis.

To develop and validate a computed tomography (CT)-based radiomics nomogram for predicting locoregional failure (LRF) in patients with locally advanced non-small cell lung cancer (NSCLC) treated with definitive chemoradiotherapy (CRT).A total of 141 patients with locally advanced NSCLC treated with definitive CRT from January 2014 to December 2017 were included and divided into testing cohort (n = 100) and validation (n = 41) cohort. Radiomics features were extracted from pretreatment contrast enhanced CT. The least absolute shrinkage and selection operator logistic regression was processed to select predictive features from the testing cohort and constructed a radiomics signature. Clinical characteristics and the radiomics signature were analyzed using univariable and multivariate Cox regression. The radiomics nomogram was established with the radiomics signature and independent clinical factors. Harrell's C-index, calibration curves and decision curves were used to assess the performance of the radiomics nomogram.The radiomics signature, which consisted of eight selected features, was an independent factor of LRF. The clinical predictors of LRF were the histologic type and clinical stage. The radiomics nomogram combined with the radiomics signature and clinical prognostic factors showed good performance with C-indexes of 0.796 (95% confidence interval [CI]: 0.709-0.883) and 0.756 (95% CI: 0.674-0.838) in the testing and validation cohorts respectively. Additionally, the combined nomogram resulted in better performance (p0.001) for the estimation of LRF than the nomograms with the radiomics signature (C-index: 0.776; 95% CI: 0.686-0.866) or clinical predictors (C-index: 0.641; 95% CI: 0.542-0.740) alone.The radiomics nomogram provided the best performance for LRF prediction in patients with locally advanced NSCLC, which may help optimize individual treatments.

Brain metastases (BMs) in non-small-cell lung cancer (NSCLC) patients are associated with significant morbidity and poor prognosis. Immune checkpoint inhibitors (ICIs) have resulted in a paradigm shift in the management of advanced NSCLC. However, the value of ICIs in NSCLC patients with BMs remains unclear because patients with BMs are routinely excluded in numerous prospective trials on ICIs. Here, starting from the mechanisms of ICIs for BMs, we will reveal the value of ICIs by reviewing the efficacy and adverse effects of ICIs monotherapy as well as promising combination strategies, such as combinations with chemotherapy, radiotherapy, and anti-angiogenic drugs, etc. In addition, the methods of patient selection and response assessment will be summarized to assist clinical practice and further studies.

The aim of this study is to investigate the effect of lncRNA DUXAP8 on proliferation and apoptosis of ovarian cancer cells, and to explore its potential mechanism. DUXAP8 interfering and overexpressing cell lines were constructed and the cell proliferation and apoptosis were tested. Hematoxylin–eosin, TdT-mediated dUTP nick end labeling, and immunohistochemistry were used to detect the effect of DUXAP8 on the ability of tumor formation. Quantitative real-time polymerase chain reaction and western blot were used to detect the mRNA and protein expression of miR-590-5p and YAP1, respectively. Dual luciferase assay was used to determine the target relationship between DUXAP8, miR-590-5p, and YAP1. DUXAP8 interference and miR-590-5p down-regulated cell lines were further constructed. Compared with normal ovarian cells, the expression of DUXAP8 in ovarian cancer cells was significantly increased, while the expression of miR-590-5p was decreased (p

Background Stereotactic body radiotherapy (SBRT) is the standard care for inoperable early stage non-small cell lung cancer (NSCLC). The purpose of our study was to investigate whether a prediction model based on cone-beam CT (CBCT) plus pretreatment CT radiomics features could improve the prediction of tumor control and lung toxicity after SBRT in comparison to a model based on pretreatment CT radiomics features alone. Methods A total of 34 cases of stage I NSCLC patients who received SBRT were included in the study. The pretreatment planning CT and serial CBCT radiomics features were analyzed using the imaging biomarker explorer (IBEX) software platform. Multivariate logistic regression was conducted for the association between progression-free survival (PFS), lung toxicity and features. The predictive capabilities of the models based on CBCT and CT features were compared using receiver operating characteristic (ROC) curves. Results Five CBCT features and two planning CT features were correlated with disease progression. Six CBCT features and two planning CT features were related to lung injury. The ROC curves indicated that the model based on the CBCT plus planning CT features might be better than the model based on the planning CT features in predicting lung injury. The other ROC curves indicated that the model based on the planning CT features was similar to the model based on the CBCT plus planning CT features in predicting disease progression. Conclusions Both pretreatment CT and CBCT radiomics features could predict disease progression and lung injury. A model with CBCT plus pretreatment CT radiomics features might improve the prediction of lung toxicity in comparison with a model with pretreatment CT features alone. Key points Significant findings of the study: A model with cone-beam CT radiomics features plus pre-treatment CT radiomics features might improve the prediction of lung toxicity after SBRT in stage I NSCLC patients. What this study adds In the prediction of PFS and lung toxicity in early-stage NSCLC patients treated with SBRT, CBCT radiomics could be another effective method.

Background and Objectives. Sentinel lymph node biopsy has been widely accepted as the standard procedure to assess the axillary lymph node status in breast cancer. However, more than 70% of excised sentinel lymph nodes have been found to be healthy. It may lead to unnecessary excisions and increase the incidence of postoperative complications. The aim of this study was to investigate the value of quantitative Tc-99 m sulfur colloid SPECT/CT in avoiding excessive removal of unnecessary sentinel lymph nodes in breast cancer patients. Methods. We retrospectively enrolled breast cancer patients who underwent SPECT/CT prior to sentinel lymph node biopsy. Quantification of radiotracer uptake from SPECT/CT data was performed. A radioactivity count threshold (RSPECT) using SPECT/CT was calculated for detecting metastatic sentinel lymph nodes. To localize sentinel lymph nodes exactly, we compared the positions of sentinel lymph nodes localized using SPECT/CT with positions localized surgically using an intraoperative γ-probe. Results. 491 patients were included, with a median of 3 sentinel lymph nodes/patient detected by the γ-probe and 2 sentinel lymph nodes/patient detected by SPECT/CT. As the number of sentinel lymph nodes visualized on SPECT/CT images, the metastasis incidence of lymph nodes in the ≤2 SLNs group was significantly higher than that in the >2 SLNs group (35% vs. 15%, P < 0.001 ). No metastasis was found in lymph nodes with RSPECT ≤ 30% in the >2 SLNs group, and thus, 30% (157/526) of SPECT/CT-identified nodes would avoid unnecessary removal. The positions of sentinel lymph nodes localized by SPECT/CT and γ-probe were identical in 42% (39/93) of patients. Conclusions. Quantitative Tc-99 m SC SPECT/CT imaging has the potential to preoperatively locate sentinel lymph nodes and intraoperatively avoid unnecessary sentinel lymph node biopsy.

Since the discovery of the fact that tyrosine kinase inhibitors could improve progression-free survival for patients with advanced non-small cell lung cancer compared with traditional chemotherapy, it has been extremely important to identify epidermal growth factor receptor mutation status in treatment stratification. Although lack of sufficient biopsy samples limit the precise detection of epidermal growth factor receptor mutation status in clinical practice, and it is difficult to identify the sensitive patients who confer favorable response to tyrosine kinase inhibitors. An increasing number of scholars tried to deal with these problems using methods based on the non-invasive imaging including computed tomography and PET to find the association with epidermal growth factor receptor mutation status and survival treated with tyrosine kinase inhibitor in non-small cell lung cancer. Although the conclusions have not reached a consensus, quantitative and high-throughput radiomics have brought us a new direction and might successfully help identify patients undergoing tyrosine kinase inhibitors who could get significant benefits.

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Although immunotherapy has achieved great clinical success in clinical outcomes, especially the anti-PD-1 or anti-PD-L1 antibodies, not all patients respond to anti-PD-1 immunotherapy. It is urgently required for a clinical diagnosis to develop non-invasive imaging meditated strategy for assessing the expression level of PD-L1 in tumors. In this work, a 68Ga-labeled single-domain antibody tracer, 68Ga-NOTA-Nb109, was designed for specific and noninvasive imaging of PD-L1 expression in an MC38 tumor-bearing mouse model. Comprehensive studies including Positron Emission Tomography (PET), biodistribution, blocking studies, immunohistochemistry, and immunotherapy, have been performed in differences PD-L1 expression tumor-bearing models. These results revealed that 68Ga-NOTA-Nb109 specifically accumulated in the MC38-hPD-L1 tumor. The content of this nanobody in MC38 hPD-L1 tumor and MC38 Mixed tumor was 8.2 ± 1.3, 7.3 ± 1.2, 3.7 ± 1.5, 2.3 ± 1.2%ID/g and 7.5 ± 1.4, 3.6 ± 1.7, 1.7 ± 0.6, 1.2 ± 0.5%ID/g at 0.5, 1, 1.5, 2 hours post-injection, respectively. 68Ga-NOTA-Nb109 has the potential to further noninvasive PET imaging and therapy effectiveness assessments based on the PD-L1 status in tumors. To explore the possible synergistic effects of immunotherapy combined with chemotherapy, MC38 xenografts with different sensitivity to PD-L1 blockade were established. In addition, we found that PD-1 blockade also had efficacy on the PD-L1 knockout tumors. RT-PCR and immunofluorescence analysis were used to detect the expression of PD-L1. It was observed that both mouse and human PD-L1 expressed among three types of MC38 tumors. These results suggest that PD-L1 on tumor cells affect the efficacy, but it on host myeloid cells might be essential for checkpoint blockade. Moreover, anti–PD-1 treatment activates tumor-reactive CD103+ CD39+ CD8+T cells (TILs) in tumor microenvironment.

// Bingjie Fan 1 , Pingping Fan 1, 2, 3 , Li Kong 1, 2, 3 , Xindong Sun 1, 2, 3 , Shuqiang Zhao 1, 2, 4 , Xiaorong Sun 1, 2, 4 , Zheng Fu 1, 2, 4 , Jinsong Zheng 1, 2, 4 , Li Ma 1, 2, 4 , Shijiang Wang 1, 2, 3 , Man Hu 1, 2, 3 and Jinming Yu 1, 2, 3 1 Shandong Cancer Hospital Affiliated to Shandong University, Jinan, China 2 Shandong Academy of Medical Sciences, Jinan, China 3 Departments of Radiation Oncology and Shandong Province Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, China 4 Departments of Nuclear Medicine, Shandong Cancer Hospital and Institute, Jinan, China Correspondence to: Man Hu, email: hu5770@sina.com Jinming Yu, email: sdyujinming@163.com Keywords: esophageal squamous cell carcinoma, radiotherapy, FDG PET/CT, concurrent chemoradiotherapy, local failure Received: October 15, 2016 Accepted: January 04, 2017 Published: February 22, 2017 ABSTRACT Esophageal squamous cell carcinoma (ESCC) patients are at risk for local failure (LF) following treatment. Predicting tumor regions at high risk for local failure before radiotherapy may increase treatment efficacy by permitting an escalated radiation dose specifically to those regions critical for tumor control. Forty-one patients with non-resectable locally advanced ESCC underwent 18 F-deoxyglucose positron emission tomography/computed tomography (FDG PET/CT) imaging before concurrent chemoradiotherapy (CCRT). After CCRT, a second (failure) FDG PET/CT was performed in cases of relapse. Failure FDG PET/CT scans were fused to pre-treatment scans to identify tumor regions at high risk for LF. Within a median follow-up time of 26 months, 20 patients (48.8%) had LF. In 19 patients, the failure occurred within a pre-treatment high FDG uptake region; the failure occurred outside these regions in only one patient. Pre-treatment metabolic tumor volume (MTV) was independently associated with LF ( P

// Xinzhe Dong 1, 2 , Xiaorong Sun 3 , Xianguang Zhao 1 , Wanqi Zhu 1 , Lu Sun 4 , Yong Huang 3 , Wenwu Li 3 , Honglin Wan 5 , Ligang Xing 1, 2 , Jinming Yu 1, 2 1 Department of Radiation Oncology, Shandong Cancer Hospital, Shandong University, Jinan, Shandong, China 2 Key Laboratory of Radiation Oncology of Shandong Province, Shandong Academy of Medical Sciences, Jinan, Shandong, China 3 Department of Radiology, Shandong Cancer Hospital and Institute, Jinan, Shandong, China 4 Jinan University, Jinan, Shandong, China 5 College of Physics and Electronic Science, Shandong Normal University, Jinan, Shandong, China Correspondence to: Ligang Xing, email: sdcancerhospital@163.com Keywords: positron emission tomography, FDG, esophageal carcinoma, intratumoral heterogeneity, prognosis Received: July 18, 2016 Accepted: January 10, 2017 Published: January 19, 2017 ABSTRACT Objective: To evaluate the impact of intratumoral metabolic heterogeneity measured by 18F-FDG PET imaging on postoperative recurrence and survival for patients with esophageal squamous cell carcinoma (ESCC). Results: AUC-CSH, metabolic tumor volume and pN-stage were significant prognostic factors for RFS. Additionally, tumor recurrence of the low AUC-CSH group (≤ 0.478) was 3 times higher than high group ( P = 0.015). The median OS of patients with advanced AJCC stage or low AUC-CSH was also significantly shorter than that of patients with stage I & II or high AUC-CSH ( P = 0.021, 0.009). Multivariate analysis identified the AUC-CSH to be the only significant risk factor for postoperative recurrence and overall survival in whole-group and stage III patients. Materials and Methods: 116 ESCC patients who underwent staging 18F-FDG PET-CT scan and surgical resection were reviewed. The metabolic parameters were assessed as follows: maximum standardized uptake value (SUV max ), metabolic tumor volume, and the area under the curve of the cumulative SUV-volume histogram (AUC-CSH), which is known to reflect the intratumoral metabolic heterogeneity. Regression analyses were used to identify clinicopathological and imaging variables associated with relapse-free survival (RFS) and overall survival (OS). Conclusions: Intratumoral metabolic heterogeneity characterized by AUC-CSH can predict postoperative recurrence and survival in patients with resectable ESCC.

Local tumor recurrence is one of the main causes for the failure of esophageal cancer treatment following radiotherapy. Previous studies have demonstrated that epidermal growth factor receptor (EGFR)‑targeted therapy combined with radiotherapy is expected to become an effective means to control tumor recurrence. The aim of the present study was to investigate the effect and mechanism of nimotuzumab (an EGFR‑targeted antibody) in the treatment of recurrent esophageal carcinoma. The radiation responses of two esophageal squamous carcinoma cell lines, EC109 and TE‑1, with or without nimotuzumab, were first evaluated by CCK‑8 assay. Colony formation and apoptosis were used to measure anti‑proliferation effects. It was demonstrated that nimotuzumab arrested the cell cycle at the G2 phase in vitro. Western blotting and immunofluorescence analysis were used to determine signaling pathway changes. It was observed that nimotuzumab inhibited phosphorylation of EGFR in EC109 cells. Furthermore, recurrent tumor models were established and it was identified that the degree of tumor hypoxia was positively associated with EGFR overexpression. In EC109 cell xenografts, nimotuzumab combined with radiation led to a significant delay in recurrent tumor growth compared with that of radiation alone (P

PURPOSE Brain metastasis (BM) is the primary first failure pattern in patients with curatively resected locally advanced non-small cell lung cancer (LA-NSCLC). It is not yet possible to accurately predict the occurrence of BM. The purpose of the research is to develop and validate a prediction model of BM-free survival based on radiomics characterising the primary lesions combined with clinical characteristics in patients with curatively resected LA-NSCLC. METHODS This study consisted of 124 patients with curatively resected stage IIB-IIIB NSCLC in our institution between January 2014 and June 2018. Patients were randomly divided into training and validation cohorts using a 4:1 ratio. Radiomics features were selected from the chest CT images before surgery. A radiomics signature was constructed using the LASSO algorithm based on the training cohort. Clinical model was developed using the Cox proportional hazards model. The clinical, radiomics, and integrated nomograms were constructed. The prediction performance of the models was assessed based on its discrimination, calibration, and clinical utility. RESULTS The radiomics signature is significantly associated with BM-free survival in the overall cohort. The discrimination performance of the integrated nomogram, with the C-indexes 0.889 (0.872-0.906, 95 % CI) and 0.853 (0.788-0.918, 95 % CI) in the training and validation cohorts, respectively, is significantly better than the clinical nomogram (p < 0.0001 for the training cohort, p = 0.0008 for the validation cohort). Compared with the radiomics nomogram, the integrated nomogram is also improved to varying degrees, but not apparent in the validation cohort (p = 0.0007 for the training cohort, p = 0.0554 for the validation cohort). The calibration curve and decision curve analysis demonstrated that the integrated nomogram exceeded the clinical or radiomics nomograms in predicting BM-free survival. CONCLUSIONS Compared with the clinical or radiomics nomograms, the predictive performance of the integrated nomogram is significantly improved. The integrated nomogram is most suitable for predicting BM-free survival in patients with curatively resected LA-NSCLC.

There are few effective treatment options for radiation-induced dermatitis in breast cancer patients. We conducted a single-arm trial to tested the hypothesis that topical epigallocatechin-3-gallate (EGCG) is effective against radiation-induced dermatitis in breast cancer patients undergoing radiotherapy. Forty-nine patients participated in this study. The patients underwent mastectomy followed by adjuvant radiotherapy. Topical EGCG was applied daily, starting when grade I dermatitis appeared and ending two weeks after radiotherapy. The maximum dermatitis observed during the EGCG treatment was as follows: Grade 1 toxicity, 71.4% (35 patients); grade 2 toxicity, 28.6% (14 patients); there were no patients with grade 3 or 4 toxicity. The majority of the radiation-induced dermatitis was observed 1 week after the end of radiotherapy. EGCG reduced the pain in 85.7% of patients, burning-feeling in 89.8%, itching in 87.8%, pulling in 71.4%, and tenderness in 79.6%. These findings suggest topical EGCG may be an effective treatment for radiation-induced dermatitis and has acceptable toxicity.

This study explored whether integrated texture parameter (ITP) of the fluorine-18-fluorodeoxyglucose PET (F-FDG PET) is a stratification factor for the survival of nonoperative patients with locally advanced non-small-cell lung cancer (LA-NSCLC).Thirty-five patients with LA-NSCLC treated with chemoradiotherapy or radiotherapy were included in the retrospective study. Eight principal components (PCs) were extracted from 72 F-FDG PET texture features (TFs) using PC analysis. The survival rates between PC subgroups (group by median value) were compared using Kaplan-Meier method. Seventy-two factor loadings for PC7 were evaluated using t-test. Standardized values of the TFs with significant factor loading were multiplied by the corresponding PC7 component coefficient, and the products were added together to obtain ITP. The survival rates between ITP subgroups (group by median value) were compared using Kaplan-Meier method. Patient characteristics between ITP subgroups were compared using χ -test, Mann-Whitney U-test, or t-test.The median follow-up time was 20.7 months. The median overall survival (OS) and progression-free survival (PFS) were 32.5 and 14.4 months, respectively. The patients with high PC7 value had lesser OS (P=0.006) and PFS (P=0.010) than those with lower value. Factor loadings of standardized uptake value kurtosis, run percentage, and zone percentage were significant for PC7 (P0.01). The patients with high ITP value had lesser OS (P=0.001) and PFS (P=0.002) than those with lower value. There were no significant differences in patient characteristics between ITP subgroups (P0.2).This study demonstrated that ITP might be a stratification factor for the survival of nonoperative patients with LA-NSCLC.

Bortezomib, a novel proteasome inhibitor, has been approved for treating multiple myeloma and mantle cell lymphoma and studied pre-clinically and clinically for solid tumors. Preferential cytotoxicity of bortezomib was found toward hypoxic tumor cells and endothelial cells in vitro. The purpose of this study is to investigate the role of a pretreatment hypoxic tumor microenvironment on the effects of bortezomib in vitro and ex vivo, and explore the feasibility of dynamic contrast enhanced magnetic resonance imaging (DCE MRI) to noninvasively evaluate the biological effects of bortezomib. It was shown in vitro by Western blot, flow cytometry, and ELISA that bortezomib accumulated HIF-1α in non-functional forms and blocks its hypoxia response in human colorectal cancer cell lines. Ex vivo experiments were performed with fluorescent immunohistochemical staining techniques using multiple endogenous and exogenous markers to identify hypoxia (pimonidazole, HRE-TKeGFP), blood flow/permeability (Hoechst 33342), micro-vessels (CD31 and SMA), apoptosis (cleaved caspase 3) and hypoxia response (CA9). After bortezomib administration, overall apoptosis index was significantly increased and blood perfusion was dramatically decreased in tumor xenografts. More importantly, apoptosis signals were found preferentially located in moderate and severe pretreatment hypoxic regions in both tumor and endothelial cells. Meanwhile, DCE MRI examinations showed that the tumor blood flow and permeability decreased significantly after bortezomib administration. The present study revealed that bortezomib reduces tumor hypoxia response and blood perfusion, thus, presenting antivascular properties. It will be important to determine the hypoxic/perfusion status pre- and during treatment at further translational studies.

In this paper, the hemoglobin (Hb) re-released from red blood cells (RBCs) and whole blood of 7 carcinoma patients were studied by using electrophoresis release test (ERT), which was established by our lab. Among the 7 carcinoma patients, the re-released Hb was distinctively increased from an intrahepatic bile duct carcinoma patient during one-dimension isotonic ERT. Different from the others, the result of double-dimension Hb re-release of this intrahepatic bile duct carcinoma patient showed that not only HbA but also HbA2 could be re-released from both RBCs and whole blood. The result of isotonic & hypotonic ERT which was performed at room temperature showed that more Hb could be re-released from both RBCs and whole blood of the intrahepatic bile duct carcinoma patient than that of the normal control. After keeping the samples at 37°C for 1 hour, the re-released Hb from RBCs could still be found more than that of the normal control, but was disappeared completely from the whole blood sample. To our surprise, when the isotonic & hypotonic ERT was repeated 2 days later at 37°C, the re-released Hb from RBCs of the intrahepatic bile duct carcinoma patient was increased only in tube 4-6, and disappeared in the other tube. Further mechanism research work cannot be continued because of the patient's leave, but ERT is speculated to be a useful and effective technology to observe the physiological or pathological change of RBCs, blood or body in the future.

Background Acute radiation-induced esophagitis (ARIE) is one of main toxicities complicated by thoracic radiotherapy, influencing patients' quality of life and radiotherapy proceeding seriously. It is difficult to be cured rapidly so far. Our phase I trial preliminarily showed that EGCG may be a promising strategy in the treatment of ARIE. Materials and methods We prospectively enrolled patients with stage III lung cancer from the Shandong Tumor Hospital & Institute in China from January 2013 to September 2014. All patients received concurrent or sequential chemo-radiotherapy, or radiotherapy only. EGCG was administrated once ARIE appeared. EGCG was given with the concentration of 440μmol/L during radiotherapy and additionally two weeks after radiotherapy. RTOG score, dysphagia and pain related to esophagitis were recorded every week. Results Thirty-seven patients with stage IIIA and IIIB lung cancer were enrolled in this trial. In comparison to the original, the RTOG score in the 1st, 2nd, 3rd, 4th, 5th week after EGCG prescription and the 1st, 2nd week after radiotherapy decreased significantly ( P =0.002, 0.000, 0.000, 0.001, 0.102, 0.000, 0.000, respectively). The pain score of each week was significantly lower than the baseline ( P =0.000, 0.000, 0.000, 0.000, 0.006, 0.000, 0.000, respectively). Conclusion This trial confirmed that the oral administration of EGCG is an effective and safe method to deal with ARIE. A phase III randomized controlled trial is expected to further corroborate the consequence of EGCG in ARIE treatment.

Background There is an urgent need for rapid and accurate microbiological diagnostic assay for detection of Clostridium difficile infection (CDI). We assessed the diagnostic accuracy of the Xpert Clostridium difficile assay (Xpert CD) for the diagnosis of CDI. Methods We searched PubMed, EMBASE, and Cochrane Library databases to identify studies according to predetermined criteria. STATA 13.0 software was used to analyze the tests for sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and area under the summary receiver operating characteristic curves (AUC). QUADAS-2 was used to assess the quality of included studies with RevMan 5.2. Heterogeneity in accuracy measures was tested with Spearman correlation coefficient and Chi-square. Results A total of 22 studies were included in the meta-analysis. The pooled sensitivity (95% confidence intervals [CI]) was 0.97 (0.95-0.99) and specificity was 0.95 (0.94-0.96). The AUC was 0.99 (0.97-0.99). Significant heterogeneity was observed when we pooled most of the accuracy measures of selected studies. Conclusions The Xpert CD assay is a useful diagnostic tool with high sensitivity and specificity in diagnosing toxigenic CDI, and this method has excellent usability due to its rapidity and simplicity.

The hypoxic microenvironment, an important feature of human solid tumors but absent in normal tissue, may provide an opportunity for cancer-specific gene therapy. The purpose of the present study was to investigate whether hypoxia-driven triple suicide gene TK/CD/UPRT expression enhances cytotoxicity to ganciclovir (GCV) and 5-fluorocytosine (5-FC), and sensitizes human colorectal cancer to radiation in vitro and in vivo. Stable transfectant of human colorectal HCT8 cells was established which expressed hypoxia-inducible vectors (HRE-TK/eGFP and HRE-CD/UPRT/mDsRed). Hypoxia-induced expression/function of TK, CD and UPRT was verified by western blot analysis, flow cytometry, fluorescent microscopy and cytotoxicity assay of GCV and 5-FC. Significant radiosensitization effects were detected after 5-FC and GCV treatments under hypoxic conditions. In the tumor xenografts, the distribution of TK/eGFP and CD/UPRT/mDsRed expression visualized with fluorescence microscopy was co-localized with the hypoxia marker pimonidazole positive staining cells. Furthermore, administration of 5-FC and GCV in mice in combination with local irradiation resulted in tumor regression, as compared with prodrug or radiation treatments alone. Our data suggest that the hypoxia-inducible TK/GCV+CDUPRT/5-FC triple suicide gene therapy may have the ability to specifically target hypoxic cancer cells and significantly improve the tumor control in combination with radiotherapy.

Background and purpose Patients with unresectable stage III non-small-cell lung cancer receiving concurrent chemoradiotherapy often develop esophagitis that may lead to unplanned treatment interruptions, which may severely reduce rates of locoregional tumor control and survival. No effectivetreatment that would reduce the incidence and severity of this complication has been identified up to now. Although acceleration of normal tissue protection using epigallocatechin-3-gallate (EGCG) has been reported, its actual clinical practicability remains obscure. Methods and materials This is a phase I study of EGCG in combination with standard chemoradiation in surgically unresectable stage III non-small-cell lung cancer. Chemotherapy (cisplatin and etoposide) was given concurrently with radiation. EGCG solution was swallowed three times a day after the occurrence of grade 2 esophagitis at six concentration levels and dose escalation followed a standard phase I design. Esophageal toxicity and patient-reported pain was recorded weekly. Results Twenty-four patients with AJCC stage IIIA (six) and IIIB (eighteen) completed the course of therapy. Twelve had squamous histology, ten adenocarcinoma, and two not specified. Patients were treated in six cohorts at six dose levels of EGCG. RT was not interrupted with a median dose of 64Gy. There were no dose-limiting toxicities reported in all EGCG dosing tiers. Dramatic regression of esophagitis to grade 0/1 was observed in 22 of 24 patients, whereas grade 2 esophagitis persisted in 2 of 24 patients at the end of radiotherapy. The pain score was also reduced from a mean of 4.58 ( N =24), 1.29 ( N =24), 1.42 ( N =24), 0.96 ( N =23) to 1.13 ( N =16) every week in turn. Conclusion We conclude that the oral administration of EGCG is feasible, safe and effective. The phase II recommended concentration is 440μmol/L.

Gene-directed enzyme prodrug therapy (GDEPT), or suicide gene therapy, has shown promise in clinical trials. In this preclinical study using stable cell lines and xenograft tumor models, we show that a triple-suicide-gene GDEPT approach produce enhanced therapeutic efficacy over previous methods. Importantly all the three genes (thymidine kinase, cytosine deaminase, and uracil phosphoribosyltransferase) function simultaneously as effectors for GDEPT and markers for multimodality molecular imaging (MMI), using positron-emission-tomography (PET), magnetic resonance-spectroscopy (MRS), and optical (fluorescent and bioluminescent) techniques. It was demonstrated that MMI can evaluate the distribution and function/activity of the triple-suicide-gene. The concomitant expression of these genes significantly enhances prodrug cytotoxicity and radiosensitivity in vitro and in vivo.

OBJECTIVE To explore the relationship of a new PET image parameter, (18)F-fluorodeoxyglucose ((18)F-FDG) uptake heterogeneity assessed by texture analysis, with maximum standardized uptake value (SUV(max)) and tumor TNM staging. MATERIALS AND METHODS Forty consecutive patients with esophageal squamous cell carcinoma were enrolled. All patients underwent whole-body preoperative (18)F-FDG PET/CT. Heterogeneity of intratumoral (18)F-FDG uptake was assessed on the basis of the textural features (entropy and energy) of the three-dimensional images using MATLAB software. The correlations between the textural parameters and SUV(max), histological grade, tumor location, and TNM stage were analyzed. RESULTS Tumors with higher SUV(max) were seen to be more heterogenous on (18)F-FDG uptake. Significant correlations were observed between T stage and SUV(max) (r(s)=0.390, P=0.013), entropy (rs=0.693, P

The prognostic importance of theAll published English-language studies that assessed the treatment response after SBRT in patients with early-stage NSCLC usingAfter evaluating the original articles, 11 retrospective studies (1008 patients) were included into the meta-analysis. Data were available in 11 studies for pre-SBRT primary tumour SUVPatients with high levels of pre-SBRT SUV

Introduction To observe the early change of metabolic tumor heterogeneity during chemoradiotherapy and to determine its prognostic value for patients with locally advanced non-small cell lung cancer (NSCLC). Methods From January 2007 to March 2010, 58 patients with NSCLC were included who were received 18F-fluorodeoxyglucose (18F-FDG) PET/CT before and following 40 Gy radiotherapy with the concurrent cisplatin-based chemotherapy (CCRT). Primary tumor FDG uptake heterogeneity was determined using global and local scale textural features extracted from standardized uptake value (SUV) histogram analysis (coefficient of variation [COV], skewness, kurtosis, area under the curve of the cumulative SUV histogram [AUC-CSH]) and normalized gray-level co-occurrence matrix (contrast, dissimilarity, entropy, homogeneity). SUVmax and metabolic tumor volume (MTV) were also evaluated. Correlations were analyzed between parameters on baseline or during treatments with tumor response, progression-free survival (PFS), and overall survival (OS). Results Compared with non-responders, responders showed significantly greater pre-treatment COV, contrast and MTV (AUC = 0.781, 0.804, 0.686, respectively). Receiver-operating-characteristic curve analysis showed that early change of tumor textural analysis serves as a response predictor with higher sensitivity (73.2%~92.1%) and specificity (80.0%~83.6%) than baseline parameters. Change in AUC-CSH and dissimilarity during CCRT could also predict response with optimal cut-off values (33.0% and 28.7%, respectively). The patients with greater changes in contrast and AUC-CSH had significantly higher 5-year OS (P = 0.008, P = 0.034) and PFS (P = 0.007, P = 0.039). In multivariate analysis, only change in contrast was found as the independent prognostic factor of PFS (HR 0.476, P = 0.021) and OS (HR 0.519, P = 0.015). Conclusions The metabolic tumor heterogeneity change during CCRT characterized by global and local scale textural features may be valuable for predicting treatment response and survival for patients with locally advanced NSCLC.

Background The identification of surgical non-small cell lung cancer (NSCLC) patients with poor prognosis is a priority in clinical oncology because of their high 5-year mortality. This meta-analysis explored the prognostic value of maximal standardized uptake value (SUVmax), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) on disease-free survival (DFS) and overall survival (OS) in surgical NSCLC patients. Materials and Methods MEDLINE, EMBASE and Cochrane Libraries were systematically searched until August 1, 2015. Prospective or retrospective studies that evaluated the prognostic roles of preoperative 18F-FDG PET/CT with complete DFS and OS data in surgical NSCLC patients were included. The impact of SUVmax, MTV or TLG on survival was measured using hazard ratios (HR). Sub-group analyses were performed based on disease stage, pathological classification, surgery only and cut-off values. Results Thirty-six studies comprised of 5807 patients were included. The combined HRs for DFS were 2.74 (95%CI 2.33–3.24, unadjusted) and 2.43 (95%CI: 1.76–3.36, adjusted) for SUVmax, 2.27 (95%CI 1.77–2.90, unadjusted) and 2.49 (95%CI 1.23–5.04, adjusted) for MTV, and 2.46 (95%CI 1.91–3.17, unadjusted) and 2.97 (95%CI 1.68–5.28, adjusted) for TLG. The pooled HRs for OS were 2.54 (95%CI 1.86–3.49, unadjusted) and 1.52 (95%CI 1.16–2.00, adjusted) for SUVmax, 2.07 (95%CI 1.16–3.69, unadjusted) and 1.91 (95%CI 1.13–3.22, adjusted) for MTV, and 2.47 (95%CI 1.38–4.43, unadjusted) and 1.94 (95%CI 1.12–3.33, adjusted) for TLG. Begg’s test detected publication bias, the trim and fill procedure was performed, and similar HRs were obtained. The prognostic role of SUVmax, MTV and TLG remained similar in the sub-group analyses. Conclusions High values of SUVmax, MTV and TLG predicted a higher risk of recurrence or death in patients with surgical NSCLC. We suggest the use of FDG PET/CT to select patients who are at high risk of disease recurrence or death and may benefit from aggressive treatments.

Clinically achievable mild temperature local hyperthermia (43 degrees C) has been demonstrated to be an effective adjuvant to radiotherapy in pre-clinical and clinical studies. In this article, we briefly review the recent progress in the following areas: (1) the effect of mild temperature hyperthermia (MTH) on tumour hypoxia and blood perfusion as assessed by dual marker immunohistochemistry (IHC); (2) the kinetics of MTH induced changes in tumour hypoxia; (3) the potential role of heat-induced tumour reoxygenation on radio- and chemo-sensitisation; (4) the potential role of MTH in combination with vascular targeting agents (VTAs) on tumour response; and (5) non-invasive detection of changes in tumour oxygenation and blood perfusion. It is shown that MTH, by itself or in combination with VTAs, leads to changes in tumour perfusion and oxygenation with potential for radio- and chemo-sensitisation.

Previous studies have shown that tumors less than 1 mm diameter derived from HT29 colorectal cancer cells are extremely hypoxic when grown intraperitoneally or intradermally in nude mice, whereas those of greater size (approximately 1-4 mm diameter) are not significantly hypoxic. The object of this study was to determine if digital autoradiography using the radiolabeled hypoxia imaging tracer iodo-azomycin galactopyranoside ((131)I-IAZGP) could detect hypoxia in this model.Microscopic HT29 tumors were grown as disseminated peritoneal disease and intradermally in nude mice. Tumors ranged in size from a few hundred microns to several millimeters in diameter. Animals were intravenously administered (131)I-IAZGP and pimonidazole 2 h before sacrifice. Following sacrifice, the intratumoral distribution of (131)I-IAZGP was assessed by digital autoradiography and compared with immunofluorescence microscopic images of pimonidazole binding and carbonic anhydrase IX (CAIX) expression.The distributions of (131)I-IAZGP, pimonidazole, and CAIX expression were similar. Tumors less than 1 mm diameter displayed high (131)I-IAZGP uptake; these tumors also stained strongly for pimonidazole and CAIX. Larger tumors (approximately 1-4 mm diameter) were not significantly hypoxic and had low (131)I-IAZGP accumulation.(131)I-IAZGP can detect hypoxia in microscopic tumors. Microscopic tumors are useful models for the validation of hypoxia radiotracers, and digital autoradiography is an appropriate technique for studying the distribution of hypoxia radiotracers in microscopic tumors.

Summary Purpose To compare the diagnostic efficacies of integrated 18F FDG PET/CT images and contrast-enhanced helical CT images in locoregional lymph node metastasis in the patients with non-small cell lung cancer (NSCLC). Methods From June 2005 to June 2007, 122 potentially operable patients with proven or suspected non-small cell lung cancer underwent integrated PET/CT and contrast-enhanced CT scans followed by surgical nodal staging. The results of reviewing PET/CT and enhanced CT images for the locoregional lymph node metastasis were compared in relation to pathologic findings. Results Preoperative nodal staging was compared with postoperative histopathological staging, 80% (98 of 122) of patients correctly staged, 13% (16 of 122) of patients were overstaged, and 7% (8 of 122) were understaged by PET/CT, while those values for CT were 56% (68 of 122), 26% (32 of 122), and 18% (22 of 122), respectively. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of PET/CT for lymph nodes were 86%, 85%, 85%, 64%, 95%, respectively; compared with 69%, 71%, 70%, 43%, 88% for CT (P = 0.000, 0.000, 0.000, 0.001, 0.001, respectively). 81% false-negative interpretations and 72% false-positive interpretations on CT were corrected by PET/CT. 57% false-negative interpretations and 45% false-positive interpretations on PET/CT were corrected by CT. 6 % (9 of 153) positive lymph nodes and 8% (40 of 486) negative nodes at pathology were incorrectly diagnosed both by PET/CT and CT. Conclusion Integrated PET/CT improves the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value than enhanced CT in the assessment of locoregional lymph nodes, and provides more efficient and accurate data of nodal staging, with a better effect on diagnosis and therapy in non-small cell lung cancer.

The aim of the present study was to investigate the biodistribution of (11)C-labeled-4-N-(3-bromoanilino), 6,7-dimethoxyquinazoline ((11)C-PD153035) and the relationship between accumulation of the tracer and epidermal growth factor receptor (EGFR) expression levels. Biodistribution studies of (11)C-PD153035 were performed in tumor-bearing nude mice. The amount of radioactivity in the lungs was small while concentrations were highest in the liver and intestine. From in vitro studies, the level of (11)C-PD153035 accumulation was detected in MDA-MB-468, A549, and MDA-MB-231 cells. The uptake of (11)C-PD153035 in cells was closely correlated with the EGFR expression level of cells (r(2) = 0.85; P < 0.001), and the results obtained in excised tumors were also significantly correlated (r(2) = 0.63; P = 0.003). Binding in MDA-MB-468, A549, and MDA-MB-231 tumors was reduced to background level at 60 min post injection( 11)C-PD153035 by pretreatment with cold PD153035. The present study showed that whether in vitro or ex vivo the uptake of (11)C-PD153035 closely correlated with EGFR expression levels. In contrast, blocking studies revealed specific binding in the three kinds of tumors. Thus (11)C-PD153035 may be used as a positron emission tomography tracer to yield useful information about tumors, particularly for lung cancer with different EGFR expression levels.

The aim of this study was to evaluate changes in the peripheral blood CD(4)(+) and CD(8)(+) T-lymphocyte populations following strontium-89 chloride ((89)SrCl(2)) therapy for painful bone metastases and to relate these changes to a therapeutic response. Forty-two (42) patients with painful bone metastases were treated with 148 MBq (4 mCi) of (89)SrCl(2). Blood samples were drawn before and monthly for 6 months after the treatment. CD(4)(+) and CD(8)(+) T-lymphocyte levels were measured using flow cytometry. The number of bone metastases and the pain score were used to assess the effect of therapy. Before the administration of (89)SrCl(2), the ratio of CD(4)(+) to CD(8)(+) T-lymphocytes was lower in patients with bone metastases than in the control subjects (p < 0.01); after therapy, the ratio increased up to the fourth month and then gradually declined to pretreatment levels. Responders had higher post-therapeutic ratios of CD(4)(+) to CD(8)(+) than nonresponders. There was a good correlation between the ratio of CD(4)(+) to CD(8)(+) and both the number of bone metastases and the pain score. The ratio of CD(4)(+) to CD(8)(+) T-lymphocytes correlated strongly with the response of bone metastases to (89)SrCl(2), and therefore, may be used as an indicator of (89)SrCl(2) efficacy.

BACKGROUND (11)C-4-N-(3-bromoanilino)-6,7-dimethoxyquinazoline ((11)C-PD153035) has been reported as a tracer for imaging human tumors that overexpress epidermal growth factor receptor (EGFR). However it is still unclear whether (11)C-PD153035 uptake correlates with EGFR expression levels. The objective of this study was to investigate the relationship between (11)C-PD153035 accumulation and EGFR expression levels. METHODS Synthesis of (11)C-PD153035 was performed in the Tracerlab FXc system. Accumulation of (11)C-PD153035 by MDA-MB-468, A549 and MDA-MB-231 cells was measured in vitro. There were six tumor-bearing mice in each group. (11)C-PD153035 uptake in tumors was determined by positron emission tomography/computed tomography (PET/CT). Tumor/normal muscle tissue (T/NT) analysis in PET images was applied to quantify the PET data. Sixty minutes after PET/CT scanning, the nude mice were sacrificed and the tumors were excised. The (11)C-PD153035 accumulation in different tumors was determined by a gamma counter. RESULTS Close correlation existed between the uptake and the level of EGFR expression both in vitro and ex vivo (r(2) = 0.72, P < 0.001; r(2) = 0.63, P = 0.003). When the static T/NT analysis method was applied to analyze the PET data, the observed correlation was again excellent (r(2) = 0.70, P = 0.001). CONCLUSIONS The uptake of PET tracer (11)C-PD153035 closely correlates with the EGFR expression levels in tumor cells. (11)C-PD153035 has the potential to yield useful information for both cancer diagnosis and therapy.

The purpose of this study was to investigate the safety, tolerability and preliminary effectiveness of topical epigallocatechin-3-gallate (EGCG) for radiation dermatitis in patients with breast cancer receiving adjuvant radiotherapy.Patients with breast cancer who received radiotherapy to the chest wall after mastectomy were enrolled. EGCG solution was sprayed to the radiation field from the initiation of Grade 1 radiation dermatitis until 2 weeks after completion of radiotherapy. EGCG concentration escalated from 40 to 660 μmol l(-1) in 7 levels with 3-6 patients in each level. EGCG toxicity was graded using the NCI (National Cancer Institute Common Terminology Criteria for Adverse Events) v. 3.0. Any adverse eventGrade 1 attributed to EGCG was considered dose-limiting toxicity. The maximum tolerated dose was defined as the dose level that induced dose-limiting toxicity in more than one-third of patients at a given cohort. Radiation dermatitis was recorded weekly by the Radiation Therapy Oncology Group scoring and patient-reported symptoms.From March 2012 to August 2013, 24 patients were enrolled. Acute skin redness was observed in 1 patient and considered to be associated with the EGCG treatment at 140 μmol l(-1) level. Three more patients were enrolled at this level and did not experience toxicity to EGCG. The dose escalation stopped at 660 μmol l(-1). No other reported acute toxicity was associated with EGCG. Grade 2 radiation dermatitis was observed in eight patients during or after radiotherapy, but all decreased to Grade 1 after EGCG treatments. Patient-reported symptom scores were significantly decreased at 2 weeks after the end of radiotherapy in pain, burning, itching and tenderness, p 0.05.The topical administration of EGCG was well tolerated and the maximum tolerated dose was not found. EGCG may be effective in treating radiation dermatitis with preliminary investigation.EGCG solution seemed to be feasible for treating radiation dermatitis in patients with breast cancer after mastectomy. It should be tested as a way to reduce radiation-induced normal tissue toxicity and complications in future years.

Neoadjuvant chemotherapy has been established as standard treatments for advanced breast cancer among multidisciplinary therapies. A simple and instructive biomarker for the postoperative recurrence and metastasis is needed to evaluate the therapeutic effect. Plasma fibrinogen level has been shown to be associated with tumor progression and poor outcomes in breast cancer patients. This study aims to further evaluate the clinical and prognostic value of plasma fibrinogen level as a biomarker in breast cancer patients receiving neoadjuvant chemotherapy. In this study, data of 67 patients were retrospectively collected and analyzed to identify the relationship between the plasma fibrinogen level and the clinical progression and outcome of these patients. Patients with increased plasma fibrinogen level after neoadjuvant chemotherapy had significantly shorter disease-free survival and overall survival (p < 0.001 and p = 0.001, respectively). In a univariate survival analysis, molecular type (p = 0.0004/p = 0.005), clinical response (p = 0.008/p = 0.015), and changes in plasma fibrinogen level (p = 0.012/p = 0.007) were associated with disease-free survival and overall survival, and all of them, molecular type (p = 0.0003/p = 0.005), clinical response (p = 0.027/p = 0.021), and changes in plasma fibrinogen level (p = 0.035/p = 0.025), were associated with disease-free survival and overall survival in a multivariate survival analysis, respectively. The plasma fibrinogen level was found to be a possible biomarker for clinical response to chemotherapy and postoperative metastasis or death in advanced breast cancer patients who received neoadjuvant chemotherapy.

Hepatoid adenocarcinoma of the stomach (HAS) is a rare distinct variant of gastric carcinoma with earlier metastases and worse prognosis compared to the more common intestinal types. It is often misdiagnosed as hepatocellular carcinoma, especially when primary HAS is insignificantly anatomically abnormal, produces high alpha-fetoprotein and develops early liver metastasis. In this case we show the significance of dual-time-point (18)F-fluorodeoxyglucose positron emission tomography (PET)/computed tomography (CT) in accurately diagnosing and staging HAS.

This study aims to explore whether the intra-tumour (18) F-fluorodeoxyglucose (FDG) uptake heterogeneity affects the reliability of target volume definition with FDG positron emission tomography/computed tomography (PET/CT) imaging for nonsmall cell lung cancer (NSCLC) and squamous cell oesophageal cancer (SCEC).Patients with NSCLC (n = 50) or SCEC (n = 50) who received (18)F-FDG PET/CT scanning before treatments were included in this retrospective study. Intra-tumour FDG uptake heterogeneity was assessed by visual scoring, the coefficient of variation (COV) of the standardised uptake value (SUV) and the image texture feature (entropy). Tumour volumes (gross tumour volume (GTV)) were delineated on the CT images (GTV(CT)), the fused PET/CT images (GTV(PET-CT)) and the PET images, using a threshold at 40% SUV(max) (GTV(PET40%)) or the SUV cut-off value of 2.5 (GTV(PET2.5)). The correlation between the FDG uptake heterogeneity parameters and the differences in tumour volumes among GTV(CT), GTV(PET-CT), GTV(PET40%) and GTV(PET2.5) was analysed.For both NSCLC and SCEC, obvious correlations were found between uptake heterogeneity, SUV or tumour volumes. Three types of heterogeneity parameters were consistent and closely related to each other. Substantial differences between the four methods of GTV definition were found. The differences between the GTV correlated significantly with PET heterogeneity defined with the visual score, the COV or the textural feature-entropy for NSCLC and SCEC.In tumours with a high FDG uptake heterogeneity, a larger GTV delineation difference was found. Advance image segmentation algorithms dealing with tracer uptake heterogeneity should be incorporated into the treatment planning system.

To compare glucose metabolism and chemosensitivity between recurrence within the irradiation field and metastases outside the irradiation field in the same patient using (18)F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography images (PET/CT).The (18)F-FDG PET/CT images of 43 cancer patients with both local recurrence (in-field) and distal metastases (out-field) after initial treatments were reviewed. 23 patients after definitive radiotherapy/chemoradiotherapy and 20 patients after radical surgery were assigned to a radiation group and surgery group, respectively. The tumor maximal diameter on CT and PET images (D CT and D PET), maximal SUV (SUVmax), and mean SUV (SUVmean) were measured. All the patients were administered chemotherapy, and 17 patients from the radiation group and 10 patients from the surgery group underwent PET/CT scanning within 1-2 months after the treatment. The changes in D CT, D PET, SUVmax and SUVmean for each lesion were calculated and compared between in-field and out-field tumors for both groups.In the surgery group, no significant difference was found in tumor size or FDG uptake between the local recurrence and metastases. In the radiation group, both SUVmax (7.03 ± 3.48) and SUVmean (4.33 ± 1.67) of the in-field tumors were lower than those (8.45 ± 4.34 and 5.36 ± 2.51, respectively, P 0.05) of out-field tumors. Moreover, the response extent of in-field tumors was lower than that of out-field tumors in the radiation group (P 0.05). However, in the surgery group, there was no difference in the response extent (tumor size and SUVs) between the local recurrence and metastases (P 0.05).The recurrence within the irradiation field and metastases outside the irradiation field in the same patient do not share the same biological characteristics or treatment response, with inferior glucose metabolism and chemosensitivity seen in locally recurrent tumors.

The aim of this study was to analyse the correlation between (18)F-labelled 3'-deoxy-3'-fluorothymidine ((18)F-FLT) PET/CT proliferation images and tumour angiogenesis as reflected by intratumoral microvessel density (MVD) in non-small-cell lung cancer (NSCLC) to provide a noninvasive method to predict the response to antiangiogenic therapy.A total of 68 patients with proven or suspected NSCLC underwent FLT PET/CT scans followed by surgery. PET/CT images were compared with pathology. Tumour proliferation was evaluated in terms of a Ki-67 labelling index (Ki-67 LI). MVD was determined using an anti-CD31 mAb (CD31-MVD), anti-CD34 mAb (CD34-MVD) and an anti-CD105 mAb (CD105-MVD) for each resected tumour.Tumour FLT maximum standardized uptake values (SUVmax) were significantly correlated with the Ki-67 LI and CD105-MVD (r = 0.550 and 0.633, P = 0.000 and 0.000, respectively), but were only marginally correlated with the CD31-MVD and CD34-MVD (r = 0.228 and 0.235, P = 0.062 and 0.054, respectively). The FLT PET false-negative patients had a longer median survival time than the FLT PET true-positive patients (log rank test, P = 0.012). The patients with a lower CD105-MVD had a longer median survival time than those with a higher CD105-MVD (P = 0.046), while patients with a lower CD31-MVD and CD34-MVD did not have a longer median survival time than those with a higher value (P = 0.438 and 0.187, respectively).FLT PET/CT imaging correlated with tumour angiogenesis as reflected by CD105-MVD and prognosis, and may be helpful in assessing antiangiogenic therapy of NSCLC.

To compare the diagnostic efficacies of (18)F-FLT and (18)F-FDG PET/CT in non-small-cell lung cancer (NSCLC), focusing on the correlation between FLT and FDG tumour uptake and tumour cell proliferation as indicated by the cyclin D1 labelling index.A total of 31 patients with NSCLC underwent FLT and FDG PET/CT scanning followed by surgery. PET/CT images were compared with the pathology. Tumour cell proliferation was assessed by cyclin D1 immunohistochemistry.The sensitivities of FLT and FDG PET/CT for the primary lesion were 74% and 94%, respectively (p=0.031). For N staging, 77% patients were correctly staged, 6% overstaged, 16% understaged by FLT, while the values for FDG were 77%, 16% and 6%, respectively. The sensitivity, specificity, accuracy, and positive predictive value with FLT for lymph nodes were 65%, 98%, 93% and 89%, respectively, and 85%, 84%, 84% and 52% with FDG (p0.01).Tumour SUV of FLT was significantly correlated with the cyclin D1 labelling index (r=0.644; p0.01), but the SUV of FDG was not significantly correlated (r=0.293; p0.05).In terms of N staging, FLT PET/CT resulted in understaging of more patients but overstaging of fewer patients, and for regional lymph nodes showed better specificity, accuracy and positive predictive value than FDG PET/CT in NSCLC. Tumour FLT uptake was correlated with tumour cell proliferation as indicated by the cyclin D1 labelling index, suggesting that further studies are needed to evaluate the use of FLT PET/CT for the assessment of therapy response to anticancer drugs.

To determine the cut-off standardized uptake value (SUV) on (18)F fluoro-2-deoxy-glucose (FDG) positron emission tomography/computed tomography (FDG-PET/CT) images that generates the best volumetric match to pathologic gross tumor volume (GTV(path)) for non-small-cell lung cancer (NSCLC).Fifteen patients with NSCLC who underwent FDG-PET/CT scans followed by lobectomy were enrolled. The surgical specimen was dissected into 5-7-mum sections at approximately 4-mm intervals and stained with hematoxylin and eosin. The tumor-containing area was outlined slice by slice and the GTV(path) determined by summing over all the slices, taking into account the interslice thickness and fixation-induced volume reduction. The gross tumor volume from the PET images, GTV(PET), was determined as a function of cut-off SUV. The optimal threshold or optimal absolute SUV was defined as the value at which the GTV(PET) was the same as the GTV(path).The fixation process induced a volumetric reduction to 82% +/- 10% (range, 62-100%) of the original. The maximal SUV was 10.1 +/- 3.6 (range, 4.2-18.7). The optimal threshold and absolute SUV were 31% +/- 11% and 3.0 +/- 1.6, respectively. The optimal threshold was inversely correlated with GTV(path) and tumor diameter (p0.05), but the optimal absolute SUV had no significant correlation with GTV(path) or tumor diameter (p0.05).This study evaluated the use of GTV(path) as a criterion for determining the optimal cut-off SUV for NSCLC target volume delineation. Confirmatory studies including more cases are being performed.

Tumor hypoxia is important in the development and treatment of human cancers. We have developed a novel xenograft model for studying and imaging of hypoxia-induced gene expression. A hypoxia-inducible dual reporter herpes simplex virus type 1 thymidine kinase and enhanced green fluorescence protein (HSV1-TKeGFP), under the control of hypoxia response element (9HRE), was stably transfected into human colorectal HT29 cancer cells. Selected clones were further enriched by repeated live cell sorting gated for hypoxia-induced eGFP expression. Fluorescent microscopy, fluorescence-activated cell sorting, and radioactive substrate trapping assays showed strong hypoxia-induced expression of eGFP and HSV1-tk enzyme in the HT29-9HRE cells in vitro. Sequential micropositron emission tomography (PET) imaging of tumor-bearing animals, using the hypoxic cell tracer 18F-FMISO and the reporter substrate 124I-FIAU, yielded similar tumor hypoxia images for the HT29-9HRE xenograft but not in the parental HT29 tumor. Using autoradiography and IHC, detailed spatial distributions in tumor sections were obtained and compared for the following hypoxia-associated biomarkers in the HT29-9HRE xenograft: 124I-FIAU, 18F-FMISO, Hoechst (perfusion), lectin-TRITC (functional blood vessels), eGFP, pimonidazole, EF5, and CA9. Intratumoral distributions of 124I-FIAU and 18F-FMISO were similar, and eGFP, pimonidazole, EF5, and CA9 colocalized in the same areas but not in well-perfused regions that were positive for Hoechst and lectin-TRITC. In enabling the detection of hypoxia-induced molecular events and mapping their distribution in vivo with serial noninvasive positron emission tomography imaging, and multiple variable analysis with immunohistochemistry and fluorescence microscopy, this human xenograft model provides a valuable tool for studying tumor hypoxia and in validating existing and future exogenous markers for tumor hypoxia. [Cancer Res 2008;68(20):8597–606]

This research discussed the diagnostic value of cellular quantitative analysis in head and neck tumor.We analysis quantitative parameters of 23 malignant tumors and 20 benign diseases with automated DNA image cytometry, they are the DNA Index (DI), S-phase Fraction (SPF), Proliferation Index (PI) and 5c Exceeding (5c Ex).The masculine rate of cellular quantitative analysis and conventional method are 76.92% and 50.00%. The value of SPF, PI and 5c Ex are 14.05%, 19.59% and 1.59% in malignant tumor, respectively. The parameters of SPF and PI showed distinct difference in the area of malignant tumor than the 1 cm sideward area of tumor and the edge of tumor.Automatic DNA image cytometry has higher masculine rate of malignant tumor than conventional method in early detection of tumor. The cellular quantitative parameters, such as SPF, PI and 5c Ex, are able to guide clinical work, specially in diagnosing of head and neck tumor, estimating biological character of malignant tumor and evaluating the area of excision.