Clinical Staging Of Patients Research Articles

Effects of dopaminergic drug adjustment on executive function in different clinical stages of Parkinson's disease.

BackgroundEffects of dopaminergic medication on executive function in patients with Parkinson’s disease (PD) are inconsistent.ObjectiveWe examined the effect of dopaminergic medication on executive function in 24 drug-naïve PD patients (de novo group) and in 21 PD patients on chronic dopaminergic medication (chronic medication group).MethodsPD patients without dementia were included in this study. For the de novo group patients, dopaminergic medication was initiated, and the dose was increased to improve motor symptoms. For the chronic medication group patients, dopaminergic medication was adjusted to relieve clinical problems. All participants were tested prior to and at 4–7 months after the drug initiation/adjustment. Executive function was assessed by using the Behavioral Assessment of the Dysexecutive Syndrome (BADS). Motor function was assessed by using the Unified Parkinson’s Disease Rating Scale (UPDRS; part III). Improvement in executive function was compared with a simultaneous change in levodopa equivalent doses (LED) of dopaminergic medication and with improvement in motor functions.ResultsThe mean standardized BADS scores showed no significant improvement in both the groups. In the de novo group, percent improvement in the standardized BADS scores showed a significant positive correlation with the LED, but not with percent improvement in UPDRS part III. In the chronic medication group, percent improvement in the standardized BADS scores was negatively correlated with change in the LED, but not with percent improvement in UPDRS part III. Multiple regression analysis using improvement in the standardized BADS score as a dependent variable and patient’s background factors (ie, age, education, disease duration, and motor and executive assessments at baseline) as independent variable showed that improvement in the executive assessment is significantly correlated with the LED only in the de novo group.ConclusionEffects of dopaminergic drug adjustment on executive function differ according to the patient’s clinical stage and depend on LED in de novo stage.

Multi detector computerized tomography scans aid in the staging of Head and Neck cancers

Introduction/Objectives: To assess the efficacy and correlation of MDCT scans in the clinical staging of patients with HNCs prior to therapeutic intervention. Methodology: Thirty-four HNCs were studied according to the 2005 WHO. Clinical AJCC 6th edition & radiological staging. Results: 14 Squamous Cell Carcinoma (SCC 41.2%) mean age 49.4 + 14.7 years, 13 Nasopharyngeal Carcinoma (NPC 38.2%) mean age 37.1 + 20.5 years, 3 Odontogenic Carcinoma (ODC 8.8% made up of 2 cases ameloblastic carcinoma 5.9% and 1 case of ameloblastic carcinosarcoma 2.9%). Others cases were 3 Adenocarcinoma (8.8%) and 1 Sinonasal Carcinoma NC (2.9%). Mean age insignificant according to gender (p = 0.342). Sensitivity, specificity, positive & negative predictive values and accuracy of clinical and radiological nodal involvements were: (47.4%; 80%; 61.8%; 75%; 54.5%) & (78.9%; 93.3%; 85.3%; 93.8%; 77.8%) respectively. Difference between clinical and radiological stages was statistically significant (X2= 260.8; p=0.01). There was a low but positive correlation between the clinical and radiologic stages (Pearson’s correlation r = 0.6). Conclusion: MDCT was significantly more accurate than clinical examination in the TNM of HNCs using AJCC/UICC TNM guidelines. Authors recommend MDCT as first line imaging technique in resource limited settings.

TET1 inhibits EMT of ovarian cancer cells through activating Wnt/β-catenin signaling inhibitors DKK1 and SFRP2

Epithelial ovarian cancer (EOC) is the deadliest type of ovarian cancer, but the mechanisms contributing to its tumorigenesis are not well understood. Herein, we will elucidate the role of Ten-eleven translocation 1 (TET1) in EOC development. The expression of TET1 in EOC cell lines and primary samples was examined by western blot and immunohistochemistry. The biological role of ectopic TET1 overexpression was revealed by a series of in vitro functional studies. Its downstream signaling pathway was predicted by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of microarray data. The methylation level and expression of Wnt/β-catenin signaling inhibitors Dikkopf 1 (DKK1) and secreted Fzd receptor protein 2 (SFRP2) were examined by Chromatin immunoprecipitation (ChIP) assay, Epimark™ 5hmC and 5mC level analysis and quantitative RT-PCR. Small interference RNA (siRNA) technology was used to investigate the biological roles of DKK1 and SFRP2. TET1 expression was inversely correlated with clinical stage in patients with EOC by tissue microarray (TMA). TET1 expression was undetected in 6 types of EOC cell lines. Ectopic expression of TET1 inhibited colony formation, cell migration and invasion in SKOV3 and OVCAR3 cells. Furthermore, TET1 overexpression reversed the epithelial-mesenchymal transition (EMT) process of SKOV3 cells. Mechanistically, TET1 potently inhibited canonical Wnt/β-catenin signaling by demethylating and upregulating two upstream antagonists of this pathway, SFRP2 and DKK1, which was associated with inhibition of EMT and cancer cell metastasis. This study uncovers that TET1 has potent tumor-suppressive effects in EOC by activating Wnt/β-catenin signaling inhibitors DKK1 and SFRP2.

HBXIP suppression reduces cell proliferation and migration and its overexpression predicts poor prognosis in non-small-cell lung cancer.

Emerging evidence has demonstrated that the high expression of HBXIP has been correlated with many cancers. With evaluation of the functional role of HBXIP in non-small-cell lung cancer, the primary aim of this study is to investigate the correlation between HBXIP expression and the prognosis of non-small-cell lung cancer patients. The protein levels of HBXIP were detected using western blotting in non-small-cell lung cancer cells. Cell proliferation and migration assays were measured to evaluate the function of HBXIP in non-small-cell lung cancer cells. A total of 120 non-small-cell lung cancer patients with strict follow-up and 60 adjacent non-tumor lung tissues were selected for immunohistochemical staining of the HBXIP protein. The localization of the HBXIP protein was detected in A549 non-small-cell lung cancer cells using immunofluorescence staining. The correlation between HBXIP expression and the clinicopathological features of non-small-cell lung cancer patients was analyzed by a chi-squared and Fisher's exact test. The overall survival rates of all of the non-small-cell lung cancer patients were calculated using the Kaplan-Meier method, and univariate and multivariate analyses were performed using the Cox proportional hazards regression model. In function, we showed that suppression of HBXIP decreased A549 cell proliferation and migration. HBXIP protein showed a mainly cytoplasmic staining pattern in non-small-cell lung cancer using immunohistochemical staining in paraffin-embedded non-small-cell lung cancer tissues and immunofluorescence staining in A549 cells. The HBXIP protein had strong positive staining in the non-small-cell lung cancer tissues, which was significantly higher than the percentage of adjacent non-tumor tissues. The overexpression of HBXIP was closely correlated with histological grade, clinical stage, lymph node metastasis, and lower overall survival rates of patients with non-small-cell lung cancer. Moreover, multivariate analysis suggested that HBXIP emerged as a significant independent prognostic factor along with clinical stage in patients with non-small-cell lung cancer. In conclusion, a high level of expression of HBXIP is associated with the progression of non-small-cell lung cancer and may be a useful biomarker for poor prognostic evaluation and a potential molecular therapy target for patients with non-small-cell lung cancer.

Cell proliferation markers at the invasive tumor front of oral squamous cell carcinoma: comparative analysis in relation to clinicopathological parameters of patients.

Objectives To evaluate the number of AgNORs per nucleus and the expression of Ki-67 at the tumor invasion front (TIF) in relation to clinical parameters (TNM), TIF classification and the prognosis of oral squamous cell carcinomas in an Uruguayan population.Material and Methods This study was conducted through a retrospective survey from 2000 to 2010 at the National Institute of Cancer Montevideo, Uruguay and included 40 patients. The samples were obtained from the resection of the tumor and the TIF was defined according with Bryne, et al.5 (1992). Expression of Ki-67 was assessed by the percentage of positive tumor cells and the AgNOR was recorded as the mean AgNOR (mAgNOR) and the percentage of AgNOR per nucleus (pAgNOR). All analyzes were performed by a blinded and calibrated observer.Results No statistically significant association was observed between immunostaining of Ki-67 and AgNOR with the different types of TIF, regional metastasis and patients prognosis, however it was observed an increase in Ki-67 expression associated with worse patient’s clinical staging, although not statistically significant.Conclusions Our results suggest that proliferation markers as AgNOR and Ki-67 are not prognostic markers at the tumor invasive front of carcinoma of oral squamous cell.

Expression of oxysterol pathway genes in oestrogen-positive breast carcinomas.

This study investigated whether gene expression levels of key modulators of the oxysterol signalling pathway modify the prognosis of patients with oestrogen receptor-positive (ER+) breast carcinomas via interaction with endocrine therapy. The prognosis of patients with ER+ breast carcinoma depends on several factors. Previous studies have suggested that some oxygenated forms of cholesterol (oxysterols) bind to oestrogen receptor and anti-oestrogen binding site which may deregulate cholesterol homoeostasis and influence effect of therapy. The expression levels of 70 oxysterol pathway genes were evaluated in a test set of breast carcinomas differing in ER expression. The genes differentially expressed in ER+ tumours were assessed in a comprehensive set of ER+ tumours to evaluate their clinical significance. A total of 193 primary patients with breast carcinoma were included. The transcript levels were determined by quantitative real-time polymerase chain reaction. The expression levels of 23 genes were found to be specifically dysregulated in ER+ tumours compared to ER- tumours of the test set. The expression levels of ABCG2, CYP7B1, CYP24A1, CYP39A1 and CH25H genes were found to be strongly associated with disease stage; however, none of the gene expression levels were associated with disease-free survival in patients treated with endocrine therapy. The expression of a number of oxysterol pathway genes is significantly modulated by ER expression and associated with the clinical stage of patients. However, the expression of oxysterol pathway genes was not found to modify the prognosis of ER+ patients with breast carcinoma treated with endocrine therapy.

The ralationship between SUV values in PET/CT and clinical staging of nasopharyngeal carcinoma

Objective:The purpose of this study was to research the relationship between SUVmax-T, SUVmaxN and SUVmax value in the PET/CT and clinical stage in patients of nasopharyngeal carcinoma(NPC).Method:Collect the clinical data and SUX values of Fifty-four patients.The statistical analyses were performed by SPSS21.0 statistical software for Windows and the Pearson correlation analysis was used for data analysis. Result:SUVmaxT was significantly associated with T stage and clinical stage(P<0.05);SUVmaxN was significantly associated with N stage and clinical stage(P<0.01);SUVmax was significantly associated with T stage, N stage and clinical stage(P<0.01); there was no statistically significant difference betweeen SUVmax and pathology (P>0.05). Conclusion:The SUV values in PET/CT were associated with clinical stage of nasopharyngeal carcinioma(NPC).

Interplay between ΔNp63 and miR-138-5p regulates growth, metastasis and stemness of oral squamous cell carcinoma.

TP63 acts as a master regulator in epithelia development and in the progression of various cancers, but its role in oral cancer pathogenesis remains unknown. This study aimed to explore the role of TP63 in the progression of oral squamous cell carcinoma (OSCC). This study shows that ΔNp63, the predominant isoform of TP63, is significantly upregulated in OSCC tissues and cell lines compared with their normal counterparts, and its expression is closely correlated with pathological differentiation, lymph node metastasis and clinical stage in patients with OSCC. The overexpression of ΔNp63 promotes growth, metastasis and stem-like properties in OSCC cells, and ΔNp63 depletion significantly represses OSCC cellular phenotypes in vitro and in vivo. The ΔNp63 isoform transcriptionally suppresses miR-138-5p expression; restoration of miR-138-5p expression partially abolishes the effect of upregulating ΔNp63. This study also demonstrates that miR-138-5p directly targets ΔNp63, resulting in crosstalk with ΔNp63. The correlation between ΔNp63 and miR-138-5p was further validated in OSCC tissues and was found to be significantly associated with the prognosis of patients with OSCC. Therefore, our data reveal that the interplay between ΔNp63 and miR-138-5p promotes OSCC progression by regulating cell growth, metastasis and stemness.

Significant upstaging of patients with stage I pancreatic cancer from clinical to pathologic staging.

349 Background: Clinical staging of patients with pancreatic cancer is essential to determine if neo-adjuvant treatment, surgery or palliative treatment is required. Patients with early stage disease often receive upfront surgery, where as patients with more advanced disease often receive neo-adjuvant therapy. Therefore the accuracy of clinical staging significantly influences management decisions. This study investigates the correlation between clinical and pathologic staging for patients with stage I pancreatic cancer. Methods: A retrospective review of patients with pancreatic cancer in National Cancer Data Base from 1998-2006 was preformed. The clinical stage of patients with presumed stage I disease was compared to the postoperative pathologic stage. Cox proportional hazard ratio model and regression analysis were used to determine factors associated with mortality and upstaging, respectively. Results: 1697 patients with clinical stage I pancreatic cancer were divided into two groups. Group 1 was comprised of patients who were stage I postoperatively and Group 2 was comprised of patients that were upstaged to either stage II, III or IV postoperatively. There were 704 (41%) in group 1 and 993 (59%) in group 2. Within group 2, 595 (60%) were stage II, 321 (32%) were stage III and 77 (8%) were stage IV. Patients that were upstaged after surgery had an increased risk of mortality (HR 1.414, p &lt; 0.001), whereas patients that received adjuvant chemotherapy had a decreased risk of mortality (HR 0.799, p &lt; 0.001). Compared to Grade 1 tumors, Grade 2 and 3 tumors on biopsy were most likely to be upstaged on final pathology (p &lt; 0.001). Conclusions: Patients with stage I pancreatic cancer are often candidates for upfront surgery, however this study demonstrates that a large number are upstaged on postoperative staging. Recognizing this may lead clinicians to administer neo-adjuvant treatment in a greater number of patients with early stage disease in order to optimize survival.

Overexpression of N-cadherin and β-catenin correlates with poor prognosis in patients with nasopharyngeal carcinoma.

An increasing amount of evidence demonstrates that epithelial-mesenchymal transition (EMT) is important in tumor invasion and metastases. The cell-cell adhesion molecule N-cadherin and the Wnt/β-catenin cascade protein β-catenin are two biomarkers of EMT. The present study aimed to measure the expression levels of N-cadherin and β-catenin in samples from patients with nasopharyngeal carcinoma (NPC) and evaluate their prognostic significance. N-cadherin and β-catenin mRNA was evaluated using reverse transcription-quantitative polymerase chain reaction in 26 NPC tissue samples and 8 nasopharyngeal epithelium samples. Protein expression of N-cadherin and β-catenin was also detected using immunohistochemistry in 128 archival NPC paraffin-embedded specimens. Finally, associations between clinical pathological parameters and prognostic values in NPC were evaluated. The results demonstrated that both the mRNA and protein levels of N-cadherin and β-catenin were significantly increased in NPC tissues compared with the controls. Enhanced expression of N-cadherin and β-catenin protein was strongly correlated with the status of lymph node metastasis and clinical stages in patients with NPC. Notably, high expression of N-cadherin and β-catenin proteins was significantly correlated with lower overall survival (OS) rate in patients with NPC. Finally, multivariate analysis demonstrated that expression of N-cadherin protein and clinical stages were independent prognostic factors for patients with NPC. Therefore, the present study demonstrated that N-cadherin and β-catenin expression may be used as potential prognostic biomarkers for patients with NPC.

Analisis Variasi Rekonstruksi Increment Overlapping terhadap Informasi Citra Anatomi pada Pemeriksaan MSCT Nasofaring dengan Klinis Karsinoma

Background: In Nasopharyngeal MSCT examination, the radiologist wants optimal image in order to evaluate the characteristics of the tumor, bone destruction due to a tumor, the extent of tumor invasion and the detection of regional metastases that serve as guidelines in determining the clinical stage in patients with nasopharyngeal carcinoma. So setting the scan parameters rekostruksi increments during the process multiplanar reconstruction (MPR) image on Nasopharyngeal MSC T will produce optimal images for diagnosis enforcement. Overlapping reconstruction increment is the distance between the image that has been reconstructed on the data volume that is made smaller than the size of the slice thickness is used. Selection of the reconstruction value increment overlapping usage right has an advantage in generating image anatomical information better for image noise becomes lower and accurate for diagnosing small structures, especially of hidden nasopharynx anatomy and difficult to detect. The purpose of this study was to determine the influence variation reconstruction increment overlapping to the anatomical information image on nasopharyngea MSCT l examination with the carcinoma clinical and determine the best value reconstruction increment overlapping that can provide optimal anatomical information image on nasopharyngeal MSCT examination with the clinical of carcinoma.Methods: This research was quantitative research with pre-experimental approach with one shoot case study method. This research was carried out by means of SIEMENS "SOMATOM EMOTION" - 16 slice in Installing Radiodiagnostic Hospital Dr. Soetomo Surabaya . The data in the form of a data volume of 10 patients in the sample with setting 3 mm slice thickness and reconstruction increment given the variation of the overlapping 30% of slice thickness (0.9 mm), 40% of the slice thickness (1.2 mm) and 50% of the slice thickness (1.5 mm) on MSCT nasopharyngeal examination with the clinical of carcinoma. Assessment anatomical information performed by the two respondents or reviewer. The data analysis was testing the influence with the simple linear regression tets and to determine the value of reconstruction increment overlapping optimal use friedman mean rank test.Result: The results showed a influence of variation reconstruction increment overlapping to the anatomical information image on nasopharyngeal MSCT examination with the clinical of carcinoma with a significance level of p = 0,000 (p 0.05). The best value reconstruction increment overlapping that can provide optimal anatomical information image on MSCT nasopharyngeal examination with the clinical of carcinoma is a reconstruction increment overlapping 50% of the slice thickness 3 mm (1.5 mm) with a mean rank in the axial slice and coronal slice image of 2.61.Conclution: There are influence of variation reconstruction increment overlapping to the anatomical information image on MSCT nasopharyngeal examination with the clinical of carcinoma with a significance level of p = 0,000 (p 0.05). Reconstruction increment overlapping 50% of the slice thickness 3 mm (1.5 mm) is a best value that can provide optimal anatomical information image on nasopharyngeal MSCT examination with the clinical of carcinoma.

Association between immunophenotypic markers and cytogenetic aberrations in Egyptian patients with plasma cell myeloma

Background Plasma cell myeloma is a devastating disease of clonal plasma cells that show considerable diversity both in their immunophenotypic and in their cytogenetic features. Immunophenotyping has been used widely for diagnostic and prognostic evaluation of malignant plasma cells. Aim The aim of this study was to evaluate the relationship between the immunophenotypic profile and standard prognostic factors, and also to determine the correlation between different antigenic expression and the cytogenetic aberrations as well as clinical stage in patients with plasma cell myeloma. Patients and methods A total of 31 newly diagnosed Egyptian patients with plasma cell myeloma were evaluated by multiparameter flow cytometry. Interphase fluorescence in situ hybridization was performed for detection of the expression of the 14q32 immunoglobulin H rearrangement, t(11;14), t(4;14), 13q del, and 17p del on bone marrow samples collected from the patients at diagnosis. Results Positive expression of CD19, CD20, CD13, and CD33 was detected in 38.7, 51.6, 19.4, and 12.9% of patients, whereas CD56, CD45, CD65, and CD117 were expressed in 41.9, 77.4, 9.7, and 25.8% of patients, respectively. A statistically significant correlation was found between CD13 positivity, CD56 positivity, or CD45 negativity and advanced International Staging System (P=0.011, 0.036, and 0.004, respectively). CD33-negative cases were significantly associated with absence of the 14q32 immunoglobulin H rearrangement (P=0.050) and absence of t(4;14) (P=0.018). CD45 positivity and CD13 negativity were correlated with absence of 13q del (P=0.031 and 0.011, respectively). Conclusion Immunophenotypic antigenic expression profile is associated with advanced clinical stage and absence of some cytogenetic aberrations in plasma cell myeloma.

Mediastinoscopy in Assessing Mediastinal Lymphadenopathy and Lung Disease

Background: Mediastinoscopy is the gold standard procedure for the pathological staging and diagnosis of mediastinal diseases. The aim of the study is to describe the significance of anterior cervical Mediastinoscopy in evaluating patients with mediastinal lymphadenopathy and lung parenchymal disease. Material and Methods: From January 2014 until June 2017 we conducted a retrospective study of 52 consecutive patients with mediastinal lymphadenopathy and lung parenchymal disease who underwent anterior cervical Mediastinoscopy. The main indications for cervical Mediastinoscopy were isolated mediastinal lymphadenopathy, undetermined lung mass with mediastinal lymphadenopathy, and the clinical staging of patients with lung cancer. Results: The study subjects consisted of 37 men and 15 women, aged 13 to 87 (mean age 50.8). Eight patients had mediastinoscopy for staging lung cancer, 27 patients had mediastinoscopy to diagnose isolated mediastinal lymphadenopathy, and 17 patients had mediastinoscopy for an undetermined lung parenchymal mass. Among the patients with isolated mediastinal lymphadenopathy, sarcoidosis was diagnosed in 6, tuberculosis in 9, reactive lymph nodes in 4, metastasis in 5 and lymphoma in 3. Lymph node metastasis (N2, N3) was found in 5 patients with lung cancer. There was no surgical-related mortality or morbidity. Conclusions: Mediastinoscopy is a safe and reliable procedure in diagnosing mediastinal diseases and is still the first choice among the investigative modalities in the clinical staging of bronchogenic carcinoma.

Impairment of dynamic thiol–disulphide homeostasis in patients with idiopathic Parkinson’s disease and its relationship with clinical stage of disease

ObjectiveThe aim of this study was to investigate dynamic thiol–disulphide homeostasis in patients with idiopathic Parkinson’s disease and to determine its relationship with the clinical stage as assessed by the modified Hoehn and Yahr scale. Design and methodsFifty-two patients with Parkinson’s disease (PD), diagnosed according to the United Kingdom Brain Bank Criteria for idiopathic PD, and 41 healthy individuals were included in the study. Clinical staging of patients was performed according to the Hoehn and Yahr scale. Peripheral blood samples were taken from all participants, and their native thiol and total thiol concentrations were measured using the newly developed automated method. In addition, their amount of disulphide bonds, disulphide/native thiol, disulphide/total thiol and native thiol/total thiol ratios were calculated. ResultsConsidering the data obtained from Parkinson's patients and the control group, both native thiol (-SH) and total thiol (-SH+-S-S) levels were found significantly lower in patients with Parkinson's disease. A negative and statistically significant relationship was found between both disease duration and disease stage and native thiol (-SH), total thiol (-SH+-S-S) levels and −SH/(‐SH+-S‐S‐) ratio. A positive and statistically significant relationship was found between both disease duration and stage and ‐S‐S‐/-SH and ‐S‐S‐/(‐SH+-S‐S‐) ratios. ConclusionIn patients with Parkinson's disease, dynamic thiol–disulphide homeostasis is disrupted, according to disease stage and duration. This balance, easily measured by using the newly developed automated method, can be used in monitoring disease progression. To our knowledge, our study will be the first report in the literature.

The behavioral approach system as an instrument for assessing clinical staging in patients with bipolar I disorder

Introduction: Bipolar disorder (BPD) is the sixth leading cause of disability worldwide. A staging model in BPD would be useful in order to provide the necessary information to the clinician for selecting stage-specific strategies for treatment. Multiple studies emphasize the view that the behavioral approach system (BAS) may be a relevant marker of illness onset and progression in BPD. Objective: The aim of this research study was to further explore the roles of self-reported BAS Drive, Fun Seeking and Reward Responsiveness levels in a sample of Romanian bipolar I disorder patients compared with a control group. Materials and methods: Our sample consisted of 93 subjects, divided in to 58 BPD I patients and 35 healthy controls. Consequently the BPD I group was subdivided, according to specific psychopathological clinical states such as mania, hypomania, depressive and mixed episodes, by using the Romanian version of the MINI International Neuropsychiatric Interview. The BIS/BAS self-report scale was used in order to assess the behavioral approach system. Results: Our study showed higher mean rank values of BAS score for the participants suffering from BPD I compared with healthy controls. Our data revealed increased mean rank values of BAS scores only for the participants who presented in a manic episode when compared with the depression, remission and the healthy control subgroups. High BAS Drive and BAS Reward Responsiveness scores were directly correlated with a greater number of past manic episodes, while a high BAS Fun Seeking score was indirectly correlated with the number of past episodes of depression. Conclusion: Our results contribute the current research findings regarding the BAS dysregulation theory in BPD and subscribe to the importance of measuring BAS hypersensitivity as a reliable behavioral marker for attaining a theoretically driven model for disease progression in BSD and improving therapeutic strategies for our patients.

Commentary on ‘Ultrasonography of Skin Changes in Legs with Chronic Venous Disease’

The paper by Dr. Caggiati 3 has opened a new path in this area as it provides a way to objectively evaluate the skin and subcutaneous tissue with ultrasound in patients with CVD. The ultrasound findings were impressive and in accord with previous histological descriptions. In patients with C2 with an apparently normal skin some may have ultrasonographic changes related to more advanced disease. It was suggested that such findings may separate patients with cosmetic issues from those having medical problems. This finding is valuable as it can affect the decision on treating such patients. In patients with edema and skin damage (C3eC6) the changes observed were more severe and affected most areas studied. Such findings may provide a sharper discrimination between the different CVD classes and better characterize the effects of CVD on skin and subcutaneous tissues. In our center, although we have not studied this prospectively, we have similar findings to those reported in the current paper. Dr. Caggiati also demonstrated that some of these changes detected by ultrasound can be reversed by the application of compression. This is very important, as treatment of reflux or obstruction, or both, can be studied in a more objective way. I believe that the “non-invasive ultrasound biopsy” proposed in this study can shed a different light on patients with CVD but also on other conditions such as the different clinical stages of patients with peripheral arterial disease. Furthermore, it may identify patients that are more likely to respond to the application of different types of treatment. This study was cross sectional and thus it is not known how accurately improvement or worsening of CVD can be determined. Also, the sample size was small and did not allow precise definitions in the different C classes, as the spectrum of presentation and skin changes is wide. For example, we have observed micro-edema in early CVD, extreme fibrotic changes in patients with C4b, and in a few patients dense acoustic shadowing from calcification or ossification of the subcutaneous tissues. The data from this study need to be reproduced by others and validated in a bigger prospective cohort. Ideally, the ultrasound data should be correlated with histological changes. Furthermore, it is very important that the effects of different types of treatment are evaluated in prospective longitudinal studies. In this way, the impact of these ultrasound observations can add another dimension to their clinical importance and also on monitoring the patient status.The current findings in this paper warrant further studies to better evaluate and understand the changes that occur in patients with CVD.

Determination of the predictive and prognostic values of polymorphism of some cell cycle genes in breast cancer

Aim: To investigate the influence of the polymorphic variants of CCND1 (G870A) and p73 (G4C14- to- A4T14) on the susceptibility to breast cancer development, also, to figure out their diagnostic and prognostic roles.Subjects and Methods: Blood samples were obtained from breast cancer patients and controls. Genotyping of CCND1 and p73 genes were carried out by PCR-RFLP and PCR-CTPP; respectively.Results: In comparison with the control group, CCND1 (G870A) GA and AA genotypes frequencies were significantly higher in breast cancer patients (p=0.035 and p=0.002; respectively), whereas CCND1 (G870A) GG genotype frequency was significantly lower (p&lt; 0.001). The CCND1 GA and AA genotypes significantly increased the risk for developing breast cancer compared with the GG genotype. The CCND1 (GA+AA) genotypes were significantly correlated with disease-free survival (DFS) of breast cancer patients. In comparison with the control group, p73 (G4C14/A4T14) GC/AT and AT/AT genotypes frequencies were significantly higher in breast cancer patients (p=0.013 and p=0.04; respectively), whereas p73 (G4C14/A4T14) GC/GC genotype frequency was significantly lower (p= 0.004). Â Compared with the GC/GC genotype, the p73 GC/AT and AT/AT genotypes significantly increased the risk for developing breast cancer. Beside being significantly correlated with DFS, p73 [(GC/AT)+ (AT/AT)] genotypes were indirectly correlated with tumor size, tumor pathological grade, patient's clinical stage, number of axillary lymph node involvement and Her2/neu expression.Conclusion: The GA and AA genotypes of CCND1 (G870A) polymorphism and the GC/AT and AT/AT genotypes of p73 (G4C14- to- A4T14) polymorphism can be used as diagnostic markers in breast cancer patients. The presence of the CCND1 (G870A) GA and AA genotypes and the GC/AT and AT/AT genotypes of p73 (G4C14- to- A4T14) polymorphism can increase the susceptibility to breast cancer incidence. Both of CCND1 (G870A) and p73 (G4C14- to- A4T14) polymorphisms can be used for prognosis of breast cancer patients.Â

Prediction of Lymph Node Metastasis in Patients with Bladder Cancer Using Whole Transcriptome Gene Expression Signatures

Clinical staging in patients with muscle invasive bladder cancer misses up to 25% of lymph node metastasis. These patients are at high risk for disease recurrence and improved clinical staging is critical to guide management. Whole transcriptome expression profiles were generated in 199 patients who underwent radical cystectomy and extended pelvic lymph node dissection. The cohort was divided randomly into a discovery set of 133 patients and a validation set of 66. In the discovery set features were identified and modeled in a KNN51 (K-nearest neighbor classifier 51) to predict pathological lymph node metastases. Two previously described bladder cancer gene signatures, including RF15 (15-gene cancer recurrence signature) and LN20 (20-gene lymph node signature), were also modeled in the discovery set for comparison. The AUC and the OR were used to compare the performance of these signatures. In the validation set KNN51 achieved an AUC of 0.82 (range 0.71-0.93) to predict lymph node positive cases. It significantly outperformed RF15 and LN20, which had an AUC of 0.62 (range 0.47-0.76) and 0.46 (range 0.32-0.60), respectively. Only KNN51 showed significant odds of predicting LN metastasis with an OR of 2.65 (range 1.68-4.67) for every 10% increase in score (p <0.001). RF15 and LN20 had a nonsignificant OR of 1.21 (range 0.97-1.54) and 1.39 (range 0.52-3.77), respectively. The new KNN51 signature was superior to previously described gene signatures for predicting lymph node metastasis. If validated prospectively in transurethral resection of bladder tumor samples, KNN51 could be used to guide patients at high risk to early multimodal therapy.

Neuropsychological assessment in different King's clinical stages of amyotrophic lateral sclerosis

Emerging evidence shows that cognitive deficits associated with frontal lobe dysfunction occur from early stages of amyotrophic lateral sclerosis (ALS). We aimed to assess neuropsychological functioning at different stages of ALS to further delineate the occurrence of cognitive impairment alongside the trajectory of ALS as defined by standard assessment procedures. We investigated several cognitive domains in 74 ALS patients classified into four different clinical stages of disease, according to a recently validated staging system for ALS (known as ‘King's’ system), and evaluated and compared the corresponding cognitive profiles. We found that data derived from global cognitive assessment and several executive (i.e. Frontal Assessment Battery and Trail Making Test B-A) and long-term memory (i.e. memory prose) tests were significantly different among the subsets of ALS patients, showing poorer performances with increasing clinical disability. In conclusion, our preliminary results support the notion that mainly frontotemporal abilities may be impaired during the ALS course and suggest that neuropsychological information could supplement the current clinical staging of patients. However, ALS-specific multi-domain screening instruments, which allow to correct neuropsychological scores for physical disability, should be validated in larger populations worldwide and routinely introduced in clinical practice.

Abstract P6-12-07: The benefit of preoperative chemotherapy in an underinsured Hispanic population with poor use of screening mammography

Abstract Background: Despite prospective clinical trials demonstrating the safety and effectiveness of preoperative chemotherapy for nearly 2 decades, it may still be underutilized in underserved, uninsured populations most likely to present with advanced cancers. The current study was performed to evaluate the effect of preoperative chemotherapy (PC) in a Hispanic safety net population. Methods: A retrospective review of Hispanic breast cancer patients who presented at clinical stage 2 or higher and were treated from July 2001 to February May 2015 at a safety net hospital. Sociodemographic, clinical, and treatment variables were evaluated. Surgical outcomes were evaluated. Margin status was determined for those who underwent breast conservation. Results: The average age of the 266 patients was 45 years. 93% of the patients were insured with Medicaid or uninsured (70%). Only 24% of patients underwent screening mammography. 133 underwent PC and 133 had primary operations. Patients who underwent PC presented with larger cancers (5cm vs 3.5cm, p &amp;lt; 0.001). 96% of patients in PC group were not candidates for lumpectomy at presentation. However, lumpectomy was performed more often in those who underwent PC (75% vs. 57%, p = 0.01). Re-excision for margins were necessary less often in those who underwent PC (10.3% vs 27%, p = 0.01). Patients who underwent PC were also less likely to require an ALND (33% vs 47%, p = 0.04). Despite presentation at higher average clinical stage in patients who underwent PC, at average follow up of 52 months, risk of IBTR and risk of regional recurrence were similar in the PC and no-PC groups (IBTR: 4.4% vs 3%, p = 0.99 and Regional: 1.5% vs. 1.5%, p = 0.99). Breast cancer specific survival was 86.5% in the PC group compared to 84% in the no-PC group (p = 0.68). Patients in the no-PC group were less likely to comply with recommended chemotherapy.Conclusions: In this underinsured, Hispanic population who did not use screening mammography, preoperative chemotherapy allowed many women to undergo breast conservation, undergo fewer operations, and were less likely to require ALND. Risk of local and regional recurrence is low in these patients and comparable to those who underwent primary operation. Citation Format: Komenaka IK, Djenic B, Walters J, Hsu C-H, Nodora JN, Martinez ME, Bouton M, Mehta D. The benefit of preoperative chemotherapy in an underinsured Hispanic population with poor use of screening mammography. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-12-07.