NED Group Research Articles

Adjuvant pembrolizumab (pembro) for renal cell carcinoma (RCC) across UCLA Integrated Staging System (UISS) risk groups and disease stage: Subgroup analyses from the KEYNOTE-564 study.

679 Background: Adjuvant pembro prolonged disease-free survival (DFS) for patients (pts) with RCC at increased risk of recurrence after nephrectomy in the phase 3 KEYNOTE-564 study (NCT03142334). This post hoc exploratory analysis evaluated efficacy of adjuvant pembro in pt subgroups based on UISS and disease stage. Methods: Pts with histologically confirmed clear cell RCC (pT2, Grade [G] 4 or sarcomatoid, N0, M0; pT3 or pT4, any G, N0, M0; any pT, any G, N+, M0; or M1 NED) were randomly assigned 1:1 to receive pembro 200 mg IV or placebo (pbo) every 3 weeks for ≤17 cycles (~1 y). DFS was assessed by investigator. UISS risk groups were derived retrospectively from TNM stage, Fuhrman nuclear grade, and ECOG PS. UISS groups were intermediate risk (pT2, G4, N0, M0; pT3, G1, N0, M0; or pT3, G2-4, N0, M0, ECOG 0), high risk (pT3, G2-4, N0, M0, ECOG PS 1; pT4, any G, N0, M0; or N1, M0), or M1 NED. Other subgroups were evaluated based on disease stage. Results: Baseline characteristics were balanced within subgroups. Median follow-up was 30.1 mo (range 20.8-47.5). Of 994 enrolled pts, most had UISS intermediate risk (n = 732, 73.6%; pembro n = 359; pbo n = 373); 195 pts (19.6%; pembro n = 100; pbo n = 95) had UISS high risk, and 58 pts (5.8%; pembro and pbo n = 29 each) had M1 NED. In the UISS intermediate risk group, the hazard ratio (HR) for DFS was 0.65 (95% CI, 0.48-0.88; 24-mo rates, pembro: 81.5%, pbo: 72.4%). In the UISS high-risk group, HR for DFS was 0.77 (95% CI, 0.49-1.20; 24-mo rates, pembro: 65.0%, pbo: 55.9%). In the M1 NED group, HR for DFS was 0.28 (95% CI, 0.12-0.66; 24-mo rates, pembro: 78.4%, pbo: 37.9%). DFS by disease stage is in the Table. Conclusions: Consistent with the results of the intention-to-treat (ITT) population, adjuvant pembro prolonged DFS compared with pbo for all subgroups. Results of this exploratory analysis further support the use of adjuvant pembro after nephrectomy as standard of care for pts with RCC at increased risk of recurrence. Clinical trial information: NCT03142334 . [Table: see text]

A comparative assessment of artificial and natural energy drinks in the epididymal and testicular milieu

"Artificial and natural energy drinks are both taken for increased energy, physical stamina, and alertness, although they differ in composition. This study investigated the effects of artificial and natural energy drinks on the testicular milieu in male pubertal rats. Eighteen Wistar rats were randomly divided into 3 groups of 6 rats each and all animals had access to food ad libitum. Group 1: (control) received water only; Group 2: (artificial energy drink- AED) received AED; Group 3: (natural energy drink- NED) received NED. A dose of 1.41ml/day/150g animal was administered and this lasted for 28 days. Sperm and testicular variables, biochemical parameters, and hormonal assays were carried out. There were significant decreases in the levels of testosterone, Lactate dehydrogenase, glucose, 3β-Hydroxysteroid dehydrogenase, and 17β- Hydroxysteroid dehydrogenase activities in AED and NED groups when compared to the control group. There was a marked increment in sperm abnormalities in the NED group when compared to AED and control groups. Also, the intake of AED led to an elevated level of Glucose-6-phosphate dehydrogenase compared to the control while a significant reduction was observed in the NED group when compared to the AED group. Artificial and natural energy drinks although consumed for strength and vigor distorted epididymis and testicular integrity via alteration of the testicular metabolism, lowering sperm quality and androgenic hormones in pubertal male Wistar rats. Keywords: energy drink, jaggery, sperm quality, steroidogenic enzymes, lactate dehydrogenase."

Prognostic Value of Molecular Intratumor Heterogeneity in Primary Oral Cancer and Its Lymph Node Metastases Assessed by Mass Spectrometry Imaging

Different aspects of intra-tumor heterogeneity (ITH), which are associated with the development of cancer and its response to treatment, have postulated prognostic value. Here we searched for potential association between phenotypic ITH analyzed by mass spectrometry imaging (MSI) and prognosis of head and neck cancer. The study involved tissue specimens resected from 77 patients with locally advanced oral squamous cell carcinoma, including 37 patients where matched samples of primary tumor and synchronous lymph node metastases were analyzed. A 3-year follow-up was available for all patients which enabled their separation into two groups: with no evidence of disease (NED, n = 41) and with progressive disease (PD, n = 36). After on-tissue trypsin digestion, peptide maps of all cancer regions were segmented using an unsupervised approach to reveal their intrinsic heterogeneity. We found that intra-tumor similarity of spectra was higher in the PD group and diversity of clusters identified during image segmentation was higher in the NED group, which indicated a higher level of ITH in patients with more favorable outcomes. Signature of molecular components that correlated with long-term outcomes could be associated with proteins involved in the immune functions. Furthermore, a positive correlation between ITH and histopathological lymphocytic host response was observed. Hence, we proposed that a higher level of ITH revealed by MSI in cancers with a better prognosis could reflect the presence of heterotypic components of tumor microenvironment such as infiltrating immune cells enhancing the response to the treatment.

Course of Disease and Clinical Management of Patients with Poorly Differentiated Thyroid Carcinoma.

Simple SummaryPoorly differentiated thyroid carcinoma (PDTC) represents a rare but aggressive variant of thyroid carcinoma and contributes to a significant proportion of thyroid carcinoma-associated deaths. Studies on PDTC are rare; therefore, we aim to assess the clinical course of these patients, evaluate the prognostic value of response to initial radioiodine therapy and identify risk factors for poor prognosis to optimize the clinical management of patients with PDCT.Background: In patients with poorly differentiated thyroid carcinoma, the clinical course and prognostic value of response to initial radioiodine therapy is evaluated. Methods: In 47 patients, clinical and imaging features were analyzed. Patients were stratified in no (NED), biochemical (B-ED) and structural evidence of disease (S-ED) assessed at the first diagnostic control and its impact on survival was evaluated. Further, possible risk factors for a shorter disease-specific survival rate (DSS) were analyzed. Results: In total, 17/47 patients consisted of NED, 10/47 were B-ED and 20/47 S-ED patients. At the last follow-up, 18/47 patients were NED, 2/47 patients B-ED and 27/47 patients S-ED. The median survival time was only reached for the S-ED group (median 3.9 years, 95%CI 2.8–5.1 years) and was not reached in the B-ED and NED groups. Metastases were diagnosed by a 18F-FDG-PET/CT scan in all cases and a multivariate analysis showed that the PET-positivity of metastases was the only significant predictor of DSS (p = 0.036). Conclusion: The response to initial surgery and radioiodine therapy in PDTC patients can achieve an excellent outcome and a further follow-up should be refined based on findings at the first diagnostic control. However, patients with an incomplete response and metastatic patients who become mostly radioiodine refractory show a significantly shorter survival, which makes accurate staging by 18F-FDG-PET/CT imaging crucial.

Proteomics Study on the Cerebrospinal Fluid of Patients with Encephalitis.

Objective: Label-free quantitative proteomics was applied to analyze differentially expressed proteins (DEPs) in the cerebrospinal fluid (CSF) of patients with encephalitis. The database was used to screen for possible biomarkers in encephalitis, followed by validation and preliminary investigation of the role of some DEPs in the pathogenesis of encephalitis using enzyme-linked immunosorbent assay (ELISA). Methods: We performed label-free quantitative proteomics on 16 cerebrospinal fluid samples (EM group, encephalitis with mental and behavioral disorders patients, n = 5; NED group, encephalitis without mental and behavioral disorders patients, n = 6; N group, healthy individuals, n = 5). The extracted CSF proteins were examined by mass spectrometry and enzymatic digestion and detected using protein profiling and data analysis. Interproscan was used to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the DEPs. ELISA was used to verify the changes in the levels of some DEPs in the CSF. Results: A total of 941 proteins were found to be significantly differentially expressed, including 250 upregulated DEPs and 691 downregulated DEPs. GO analysis suggested that there were six enriched functions that intersect among the EM, NED, and N groups, including synapse organization, membrane, integral component of membrane, membrane part, G-protein-coupled receptor signaling pathway, and transmembrane signaling receptor activity. KEGG analysis revealed that there were three signaling pathways that intersect among the EM, NED, and N groups, including fructose and mannose metabolism, inositol phosphate metabolism, and Jak-STAT signaling pathway. Furthermore, four downregulated encephalitis-related neurological synapse proteins were identified after screening for differentially expressed proteins, including NRXN3, NFASC, LRRC4B, and NLGN2. The result of ELISA further verified that the expression of NLGN2 and LRRC4B was obviously higher in the NED group than in the N group. Conclusions: These findings demonstrated that NLGN2 and LRRC4B proteins were upregulated in the NED group and could be potential biomarkers for the diagnosis of encephalitis, but still needs a lot of multiomics studies to be used in clinical.

Effect Of Gastrocnemius Post-exercise Needling Treatment On Achilles Tendon Tendinopathy Prevention

PURPOSE: Long-term post-exercise high intensity gastrocnemius tension can induce the Achilles tendon tendinopathy. The gastrocnemius post-exercise needling treatment can reduce gastrocnemius tension. Therefore, the gastrocnemius post-exercise needling may decrease the risk of Achilles tendon tendinopathy by reduce gastrocnemius tension. METHODS: 32 male 12 weeks old SD rats divided into 4 groups: the needling group (NED group); exercise group (EX group); exercise and needling group (EXNED group) and control group (CON group). The animal treadmill protocol was 60% average VO2max intensity (16.5m/min) eccentric running at -11° condition lasting 90 minutes for 24 days. The EXNED and NED groups accepted needling treatment with 0.25mm diameter needle which penetrate 5mm on gastrocnemius for 5 minutes after exercise each day. Gastrocnemius and Achilles tendon were harvested at the 26th day then measured collagen I/III, MMP-1, mechanical growth factor (TGF-β1, IGF-1) expression and cell apoptosis ratio by western-blot, Immunofluorescence and TUNEL staining. Data was analyzed by SPSS 20.0. RESULTS: The gastrocnemius TGF-β1 in EX group was significantly higher than other three groups (0.20±0.01 VS 0.11±0.01, 0.13±0.02, 0.14±0.01, P<0.05); IGF-1 was no significant difference. In Achilles tendon, TGF-β1 in EX group was significantly higher than other three groups (733.58±306.82 VS 291.92±156.19, 153.74±114.96, 192.67±112.36, OD/μm2, P<0.05); IGF-1 was no significantly difference either. Collagen I in EX and EXNED group were significantly lower than CON and NED group (557.26±210.54, 798.89±122.06 VS 958.59±176.41, 1133.60±251.62, OD/μm2, P<0.05); collagen III in EX group was significantly higher than other three groups (1101.25±196.37 VS 393.03±60.13, 492.25±103.16, 779.32±140.25, OD/μm2, P<0.01), and it was significantly higher in EXNED group than in CON and NED group (779.13±140.42 VS 393.17±60.15, 492.20±103.11, OD/μm2, P<0.05). The MMP-1 in the EX group was significantly higher than other three groups (624.09±176.62 VS 393.51±119.66, 264.9±78.4, 289.4±85.68, OD/μm2, P<0.05). Cell apoptosis ratio was no significant difference. CONCLUSION: The gastrocnemius post-exercise needling treatment can decrease the risk of Achilles tendon tendinopathy by reduce gastrocnemius tension.

Can emotional design really evoke emotion in multimedia learning?

The aim of this study was to investigate the effects of emotional design on learners’ performance and emotions. If emotional design has any effects on learners’ performance and emotions, then we attempted to explore dimensions that are accounted for such effects. 316 Chinese university students participated in this study. The students were divided into two groups: NED group - students in this group learned material based on neutral design, and PED group - students in this group learned material based on positive design. We explored the differences between two groups in student learning performance as well as emotion. Prior knowledge, retention, and transfer tests were also carried out and outcomes were compared across two groups. In addition, student emotion was measured using a positive affect scale and biofeedback instruments. The results showed that PED group outperformed NED group on retention and transfer tests. However, insignificant difference was found between two groups on student emotion. Our results suggest that, although the effect of emotional design was insignificant on student emotion, it was significant on student learning performance (i.e. on retention and transfer tests). Based on our results, several implications were drawn and suggestions were made for educators and researchers.

Depression Partially Mediates the Association Between Binge Eating Disorder and Health-Related Quality of Life.

Research has found that individuals with binge eating disorder (BED) report significantly worse health-related quality of life (HRQL) than those without eating disorders. Studies indicate that the association between BED and HRQL is largely accounted for by psychopathology (e.g., depression), rather than physiology [e.g., increased body mass index (BMI)]. However, to our knowledge, no study has yet investigated whether mental health symptoms could potentially mediate the relationship between BED and HRQL. To this aim, the present study compared a sample of adults who met DSM-5 criteria for BED (n = 72) recruited from the community for a treatment trial and a community sample of individuals with no history of an eating disorder (NED; n = 79). Participants completed self-report measures of HRQL (Short-Form 6D), eating disorder psychopathology (Eating Disorder Examination Questionnaire), and anxiety and depressive symptoms (Brief Symptom Inventory). Consistent with previous findings, the BED group reported significantly worse HRQL than the NED group after controlling for age, BMI, anxiety, depression, and eating disorder psychopathology. Moreover, depression partially mediated the relationship between BED diagnosis and HRQL. These results suggest that lessened HRQL may be partly explained by comorbid symptoms of depression in BED. Clinicians may find it helpful to specifically assess and treat depression in BED as a means of enhancing patients’ well-being. Future research should replicate these findings using longitudinal data that will allow for causal inferences.

An examination of emotion-related facets of impulsivity in binge eating disorder

ObjectiveWhile research suggests a positive association between negative urgency (NU) and binge eating, the association between positive urgency (PU) and binge eating has been less well studied. Moreover, few studies have examined NU and PU in binge eating disorder (BED). The present study examined Whiteside and Lynam's (2001) five facets of impulsivity (including NU and PU) in individuals with BED and a control group with no history of an eating disorder (NED). MethodCommunity samples of adults with BED (n = 72) and NED (n = 79) completed self-report measures of impulsivity, eating disorder (ED) psychopathology, and symptoms of depression and anxiety. ResultsThe only facet of impulsivity that differed between the groups was NU, with the BED group reporting significantly higher scores on NU than the NED group. Although differences in PU initially emerged, these were no longer significant after controlling for NU. None of the impulsivity subscales predicted binge frequency, but four of the five subscales (NU, perseverance, premeditation, and PU) were significantly related to ED psychopathology. DiscussionThe present findings suggest that those with BED exhibit greater NU than those without BED and that this may play role in BED symptomatology. Furthermore, the association between various impulsivity factors and ED psychopathology suggests that additional research is needed to understand these relationships in BED.

Symptoms of ‘food addiction’ in binge eating disorder using the Yale Food Addiction Scale version 2.0

‘Food addiction’ refers to the idea that certain highly palatable foods can trigger an addictive-like process in susceptible individuals. The aim of this study was to assess the prevalence and clinical significance of ‘food addiction’ symptoms in binge eating disorder (BED) using the second version of the Yale Food Addiction Scale (YFAS 2.0). Participants were 71 individuals with BED and 79 individuals with no history of an eating disorder (NED). The Eating Disorder Examination 17.0 (EDE) was used to diagnose BED and to measure binge eating. Participants completed self-report measures of eating disorder psychopathology, psychological distress, and the YFAS 2.0. Results indicated that the BED group reported significantly higher ‘food addiction’ scores compared to the NED group after controlling for relevant covariates. In fact, 92% of the BED group met YFAS 2.0 criteria for at least mild ‘food addiction’ compared to only 6% of the NED group. BED participants who met criteria for Moderate/Severe ‘food addiction’ reported significantly higher eating disorder psychopathology (except dietary restraint) as well as higher levels of anxiety and depression than BED participants with No/Mild ‘food addiction’. Scores on the YFAS 2.0 positively predicted binge frequency, but not global eating disorder psychopathology, in the BED group after controlling for body mass index (BMI), depression and anxiety. The high rate of ‘food addiction’ symptoms in the BED group may reflect overlap between the symptoms assessed by the YFAS 2.0 and the clinical features of BED. A focus on identifying overlapping and distinctive underlying mechanisms rather than similarities and differences in clinical features might be a more fruitful avenue for future research on BED and ‘food addiction’.

I weigh therefore I am: Implications of using different criteria to define overvaluation of weight and shape in binge-eating disorder.

Research suggests that overvaluation of weight and shape is a clinical feature in binge-eating disorder (BED). However, this construct has been differentially defined in the literature even when using the same measure. Here we compare two cut-offs that have previously been used to differentiate clinical and subthreshold overvaluation using the EDE-Q. Individuals with BED (n = 72, 93% female) and no history of an eating disorder (NED; n = 21, 91% female) completed measures of eating disorder (ED) and general psychopathology online. Individuals with BED were categorized as having clinical or subthreshold overvaluation using two different cut-offs used in previous studies. The clinical, subthreshold, and NED groups were compared on ED and general psychopathology. The association between overvaluation and psychopathology was also assessed in the BED and NED groups. The two cut-offs yielded identical results, with individuals in the clinical overvaluation group reporting greater ED psychopathology than those in the subthreshold and NED groups. When considered as a continuous variable, overvaluation was a significant predictor of both ED-related and general psychopathology. The two cut-offs yielded identical results, likely due to the high internal consistency between overvaluation items. Under such circumstances, the use of either cut-off seems appropriate. However, given the associations reported in the regression analyses, we propose that considering overvaluation as a dimensional variable, rather than a categorical one, may have greater utility.

An examination of the relationship between binge eating disorder and insomnia symptoms.

Although studies on sleep difficulties in binge eating disorder (BED) have produced inconsistent findings, research has linked poor sleep to the presence of related concerns (e.g., obesity, anxiety, and depression). To clarify the relationship between BED and sleep problems, this study aimed to compare insomnia symptoms in individuals with BED and those with no history of an eating disorder (NED). An adult community sample of individuals with BED (N=68) and NED (N=78) completed measures of insomnia, depression and anxiety, and eating disorder symptoms. Individuals with BED reported significantly greater insomnia symptoms than the NED group. The relationship between BED and insomnia symptoms was partially mediated by anxiety. Depression fully mediated the positive association between insomnia symptom severity and binge frequency in the BED group. These findings suggest that depression, anxiety, and sleep are important constructs to consider in BED development and presentation.

Features of papillary thyroid microcarcinoma associated with lateral cervical lymph node metastasis.

Papillary thyroid microcarcinoma (PTMC) has an excellent prognosis with an indolent disease course. However, some PTMCs have an aggressive course with lateral cervical lymph node (LCLN) metastasis or distant metastasis. This study aimed to evaluate the pre-operative features of PTMC associated with LCLN metastasis. This retrospective cohort study with a nested, matched case-control design included 199 PTMC patients with LCLN metastasis at initial surgery (N1b group) and 196 PTMC patients without any LN metastasis or persistent disease (N0 NED group) as controls; primary tumour sizes were matched. Compared with the N0 NED group, the N1b group was younger (<50 years) and more likely to be male (P = 0·002 and P = 0·003, respectively). On pre-operative neck ultrasonography (US), N1b group PTMCs were more commonly associated with a location in the upper lobes of the thyroid, or in the subcapsular area and microcalcifications than N0 NED group PTMCs (all P < 0·001). An increase in the number of these features was significantly associated with a higher risk of LCLN metastasis (P < 0·001). Evaluation of the clinical and pre-operative US characteristics of 26 patients with confirmed LCLN recurrence after initial treatment of clinical N0 PTMCs revealed that the distribution of the number of suspicious features in these patients was similar to that of the N1b group. Papillary thyroid microcarcinomas in young (<50 years) or male patients, with an upper lobe or subcapsular location, and with microcalcification have a higher risk of LCLN metastasis. Individualized management according to the number of these suspicious features may be needed for small thyroid nodules.

Risk factors for cancer recurrence or death within 6 months after liver resection in patients with colorectal cancer liver metastasis.

PurposeThe aim of this study was to find risk factors for early recurrence (ER) and early death (ED) after liver resection for colorectal cancer liver metastasis (CRCLM).MethodsBetween May 1990 and December 2011, 279 patients underwent liver resection for CRCLM at Korea University Medical Center. They were assigned to group ER (recurrence within 6 months after liver resection) or group NER (non-ER; no recurrence within 6 months after liver resection) and group ED (death within 6 months after liver resection) or group NED (alive > 6 months after liver resection).ResultsThe ER group included 30 patients (10.8%) and the NER group included 247 patients (89.2%). The ED group included 18 patients (6.6%) and the NED group included 253 patients (93.4%). Prognostic factors for ER in a univariate analysis were poorly differentiated colorectal cancer (CRC), synchronous metastasis, ≥5 cm of liver mass, ≥50 ng/mL preoperative carcinoembryonic antigen level, positive liver resection margin, and surgery alone without perioperative chemotherapy. Prognostic factors for ED in a univariate analysis were poorly differentiated CRC, positive liver resection margin, and surgery alone without perioperative chemotherapy. Multivariate analysis showed that poorly differentiated CRC, ≥5-cm metastatic tumor size, positive liver resection margin, and surgery alone without perioperative chemotherapy were independent risk factors related to ER. For ED, poorly differentiated CRC, positive liver resection margin, and surgery alone without perioperative chemotherapy were risk factors in multivariate analysis.ConclusionComplete liver resection with clear resection margin and perioperative chemotherapy should be carefully considered when patients have the following preoperative risk factors: metastatic tumor size ≥ 5 cm and poorly differentiated CRC.

Clinical significance and expression of microRNA in diabetic patients with erectile dysfunction.

The aim of the present study was to investigate the expression of microRNA (miR)-93, miR-320 and miR-16 and to assess their diagnostic value in diabetic patients with erectile dysfunction (ED). A total of 120 individuals were divided into three groups, which included the diabetics with ED group (ED group), the diabetics without ED group (NED group) and the healthy volunteers group (control group). Each group included 40 individuals. Serum samples were collected and reverse transcription quantitative polymerase chain reaction detection of the three types of miRNA was performed and the sensitivity of ED was analyzed by receiver operating characteristic curves. A negative correlation was identified between the incidence of ED in patients with diabetes and serum total testosterone levels (r=0.302, P<0.05); however, a positive correlation was observed between the incidence of ED in diabetics and the HbA1c level (r=0.231, P<0.05). Additionally, the relative expression levels of the three types of miRNA were higher in the ED group when compared with the NED and control groups (P<0.05). When compared with the control group, the area under the curve (AUC) values for miR-93, miR-320 and miR-16 were 0.793, 0.818 and 0.810, respectively, in the ED group and 0.576, 0.532 and 0.542 in the NED group, respectively. Furthermore, when compared with the NED group, the AUC value for miR-93, miR-320 and miR-16 was 0.707, 0.810 and 0.833, respectively, in the ED group. Therefore, the expression levels of miR-93, miR-320 and miR-16 may be useful for the early diagnosis of ED in patients with diabetes.

Clinical and genomic analysis of metastatic prostate cancer progression with a background of postoperative biochemical recurrence.

To better characterize the genomics of patients with biochemical recurrence (BCR) who have metastatic disease progression in order to improve treatment decisions for prostate cancer. The expression profiles of three clinical outcome groups after radical prostatectomy (RP) were compared: those with no evidence of disease (NED; n = 108); those with BCR (rise in prostate-specific antigen [PSA] level without metastasis; n = 163); and those with metastasis (n = 192). The patients were profiled using Human Exon 1.0 ST microarrays, and outcomes were supported by a median 18 years of follow-up. A metastasis signature was defined and verified in an independent RP cohort to ensure the robustness of the signature. Furthermore, bioinformatics characterization of the signature was conducted to decipher its biology. Minimal gene expression differences were observed between adjuvant treatment-naïve patients in the NED group and patients without metastasis in the BCR group. More than 95% of the differentially expressed genes (metastasis signature) were found in comparisons between primary tumours of metastasis patients and the two other outcome groups. The metastasis signature was validated in an independent cohort and was significantly associated with cell cycle genes, ubiquitin-mediated proteolysis, DNA repair, androgen, G-protein coupled and NOTCH signal transduction pathways. This study shows that metastasis development after BCR is associated with a distinct transcriptional programme that can be detected in the primary tumour. Patients with NED and BCR have highly similar transcriptional profiles, suggesting that measurement of PSA on its own is a poor surrogate for lethal disease. Use of genomic testing in patients undergoing RP with an initial rise in PSA level may be useful to improve secondary therapy decision-making.

Erectile Dysfunction among Diabetic Men in Two Medical Centers in Burkina Faso: Epidemiological, Diagnosis and Therapeutic Aspects

Objective: To study erectile dysfunction in diabetic patients seen in two clinics in the city of Bobo-Dioulasso, Burkina Faso. Materials and Methods: A prospective cross-sectional descriptive study was conducted at the Souro Sanou Teaching Hospital (CHUSS) and the Saint Leopold clinic in Bobo-Dioulasso, from March 1 to September 1, 2012. A total of 107 patients data were collated and analysed, which was then grouped into two: the ED group, designating patients with erectile dysfunction and the NED group consisting of those patients without. The sample comprised of 61 patients with types 1 and 2 diabetesand were aged between 25-70 years. The IIEF-5 was used to evaluate erectile dysfunction. Results: The prevalence of erectile dysfunction was 57%. The average age of patients was 54.4 ± 8.3 years. All patients with ED had type 2 diabetes. The mean disease duration of diabetes was 7.2 ± 6 years. Erectile dysfunction was severe in 32.8% of cases, moderate in 31.1% of cases and mild in 36.1%. Its severity was significantly associated with glycated hemoglobin, triglycerides and BMI. Phosphodiesterase types 5 (PDE5) inhibitors were found to be effective in the treatment of erectile dysfunction with a satisfactory therapeutic response in 77.4% of users. Conclusion: Erectile dysfunction is a common complication in diabetic patients. Its occurrence and severity are influenced by several factors. The potential presence of this disorder should be assessed due to its negative impact on quality of life. Phosphodiesterase type 5 inhibitors are an effective treatment modality in diabetic patients.

Apolipoprotein C-II Is a Potential Serum Biomarker as a Prognostic Factor of Locally Advanced Cervical Cancer After Chemoradiation Therapy

To determine pretreatment serum protein levels for generally applicable measurement to predict chemoradiation treatment outcomes in patients with locally advanced squamous cell cervical carcinoma (CC). In a screening study, measurements were conducted twice. At first, 6 serum samples from CC patients (3 with no evidence of disease [NED] and 3 with cancer-caused death [CD]) and 2 from healthy controls were tested. Next, 12 serum samples from different CC patients (8 NED, 4 CD) and 4 from healthy controls were examined. Subsequently, 28 different CC patients (18 NED, 10 CD) and 9 controls were analyzed in the validation study. Protein chips were treated with the sample sera, and the serum protein pattern was detected by surface-enhanced laser desorption and ionization-time-of-flight mass spectrometry (SELDI-TOF MS). Then, single MS-based peptide mass fingerprinting (PMF) and tandem MS (MS/MS)-based peptide/protein identification methods, were used to identify protein corresponding to the detected peak. And then, turbidimetric assay was used to measure the levels of a protein that indicated the best match with this peptide peak. The same peak 8918 m/z was identified in both screening studies. Neither the screening study nor the validation study had significant differences in the appearance of this peak in the controls and NED. However, the intensity of the peak in CD was significantly lower than that of controls and NED in both pilot studies (P=.02, P=.04) and validation study (P=.01, P=.001). The protein indicated the best match with this peptide peak at 8918 m/z was identified as apolipoprotein C-II (ApoC-II) using PMF and MS/MS methods. Turbidimetric assay showed that the mean serum levels of ApoC-II tended to decrease in CD group when compared with NED group (P=.078). ApoC-II could be used as a biomarker for detection in predicting and estimating the radiation treatment outcome of patients with CC.

Analysis of the risk factors for early death due to disease recurrence or progression within 1 year after hepatectomy in patients with hepatocellular carcinoma

BackgroundLiver resection for hepatocellular carcinoma (HCC) has the highest local controllability among all local treatments and results in a good survival rate. However, the recurrence rates of HCC continue to remain high even after curative hepatectomy Moreover, it has been reported that some patients with HCC have an early death due to recurrence. We analyzed the preoperative risk factors for early cancer death.MethodsBetween 1997 and 2009, 521 consecutive patients who underwent hepatectomy for HCC at our center were assigned to group ED (death due to HCC recurrence or progression within 1 year after hepatectomy) and group NED (alive over 1 year after hepatectomy). Risk factors for early cancer death were analyzed.ResultsGroup ED included 48 patients, and group NED included 473 patients. The cause of death included cancer progression (150; 78.1%), operation-related (1; 0.5%), hepatic failure (15; 7.8%), and other (26; 13.5%). Between the ED and NED groups, there were significant differences in albumin levels, Child-Pugh classifications, anatomical resections, curability, tumor numbers, tumor sizes, macroscopic vascular invasion (portal vein and hepatic vein), alpha-fetoprotein (AFP) levels, AFP-L3 levels, protein induced by vitamin K absence or antagonism factor II (PIVKA-II) levels, differentiation, microscopic portal vein invasion, microscopic hepatic vein invasion, and distant metastasis by univariate analysis. Multivariate analysis identified specific risk factors, such as AFP level > 1,000 ng/ml, tumor number ≥ 4, tumor size ≥ 5 cm, poor differentiation, and portal vein invasion. With respect to the preoperative risk factors such as AFP level, tumor number, and tumor size, 3 (1.1%) of 280 patients with no risk factors, 12 (7.8%) of 153 patients with 1 risk factor, 24 (32.9%) of 73 patients with 2 factors, and 9 (60.0%) of 15 patients with 3 risk factors died within 1 year of hepatectomy (p < 0.0001).ConclusionsHepatectomy should be judiciously selected for patients with AFP level > 1,000 ng/ml, tumor number ≥ 4, and tumor size ≥ 5 cm, because patients with these preoperative risk factors tend to die within 1 year after hepatectomy; these patients might be better treated with other therapy.

Abstract 3148A: MYOD1, hTERT, and RASSF1A gene promoter methylation is useful for prediction of outcome/ prognostication in patients with invasive cervical cancer

Abstract Background: Cervical cancer is the leading cause of cancer related mortality in women worldwide including India. DNA methylation, an epigenetic event regulates gene expression and chromatin structure. We hypothesized that the promoter methylation of genes involved in tumor suppression, DNA repair, cell cycle and apoptosis may affect response to radiation therapy and therefore the outcome of women with invasive cervical cancer. Objective: To perform DNA methylation profiling of BRCA1, RASSF1A, MLH1, ESR1, MYOD1 and hTERT genes in tissue samples of invasive cervical cancer and correlate the methylation pattern to radiation response and clinical outcome. Methodology: After obtaining informed consent, patients with invasive cervical cancer who underwent chemo-radiation as per protocol and with a minimum of 2 years follow-up after completion of treatment were included in the analysis [N=91; 2008-11]. The patients were followed up 3 monthly for evidence of local or systemic disease and their outcome documented. 60 patients were alive and well with No evidence of disease [NED] at the end of 24 months whereas 31 patients had evidence of disease [ED]. Out of these 31 patients, 3 died of disease, 9 had evidence of systemic disease [SED] and 19 patients had local disease recurrence [LED]. Genomic DNA was extracted from the snap frozen cervical biopsy tissues using TRIzol reagent, modified using the EZDNA methylation kit and promoter methylation of the individual genes determined by Real Time Polymerase Chain Reaction using Taqman probe chemistry using previously published primer and probe sets and appropriate controls. The probes were labelled with 5′-FAM and 3′-BHQ respectively. The housekeeping gene α-ACTIN was taken as the reference gene. Statistical analysis: Pearson's Chi-square test with Yates correction and Step-wise Logistic Regression was performed using the SPSS package version 18.0. A p-value &amp;lt;0.05 was considered as statistically significant. Results: In invasive cervical cancer, BRCA1, RASSF1A, MLH1, MYOD1, ESR1 and hTERT gene promoters were methylated in 51%, 47%, 40%, 51%, 38% and 60% cases respectively. Comparison of the NED vs LED groups revealed that methylated MYOD1 and hTERT genes in combination predicted for better outcome (Chi-Square test, p=0.03). Further logistic regression analysis revealed that methylation of RASSF1A, MYOD1 and hTERT genes predicted for better outcome following radiation therapy indicating that these genes play a role in determining radiation responsiveness of a tumor. The cross-classification table showed that 80% of the cases could be correctly classsified by the logistic model. Conclusion: A panel of 3 genes which includes MYOD1, hTERT and RASSF1A may be useful to predict the outcome of invasive cervical carcinoma patients treated with standard chemo-radiation therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3148A. doi:1538-7445.AM2012-3148A