One in three highly selected Greek patients with breast cancer carries a loss-of-function variant in a cancer susceptibility gene.

BACKGROUND: Gene panel testing has become the norm for assessing breast cancer (BC) susceptibility, but actual cancer risks conferred by genes included in panels are not established. Contrarily, deciphering the missing hereditability on BC, through identification of novel candidates, remains a challenge. We aimed to investigate the mutation prevalence and spectra in a highly selected cohort of Greek patients with BC, questioning an extensive number of genes, implicated in cancer predisposition and DNA repair, while calculating gene-specific BC risks that can ultimately lead to important associations. METHODS: To further discern BC susceptibility, a comprehensive 94-cancer gene panel was implemented in a cohort of 1382 Greek patients with BC, highly selected for strong family history and/or very young age (<35 years) at diagnosis, followed by BC risk calculation, based on a case-control analysis. RESULTS: Herein, 31.5% of patients tested carried pathogenic variants (PVs) in 28 known, suspected or candidate BC predisposition genes. In total, 24.8% of the patients carried BRCA1/2 loss-of-function variants. An additional 6.7% carried PVs in additional genes, the vast majority of which can be offered meaningful clinical changes. Significant association to BC predisposition was observed for ATM, PALB2, TP53, RAD51C and CHEK2 PVs. Primarily, compared with controls, RAD51C PVs and CHEK2 damaging missense variants were associated with high (ORs 6.19 (Exome Aggregation Consortium (ExAC)) and 12.6 (Fabulous Ladies Over Seventy (FLOSSIES)), p<0.01) and moderate BC risk (ORs 3.79 (ExAC) and 5.9 (FLOSSIES), p<0.01), respectively. CONCLUSION: Studying a large and unique cohort of highly selected patients with BC, deriving from a population with founder effects, provides important insight on distinct associations, pivotal for patient management.

BRCA1 and BRCA2 germline testing in Cretan isolates reveals novel and strong founder effects.

Germline BRCA1 and BRCA2 loss-of-function variants have been linked to increased breast and ovarian cancer risk, with more than 5,000 distinct pathogenic variants being reported worldwide. Among individuals of Greek descent, the BRCA1/2 variant spectrum is heterogeneous, but characterized by strong founder effects. As patients from certain geographical regions of Greece (like Crete) were underrepresented in previous studies, we hypothesized that isolated Cretans, a southern Greece islanders' population with distinct demographic, cultural and genetic features, could harbor founder BRCA1/2 mutations. A total of 304 breast or/and ovarian cancer patients of Cretan descent, fulfilling NCCN criteria for genetic testing, were tested by NGS or Sanger sequencing, followed by MLPA. Haplotype analysis was subsequently performed to investigate potential founder effects of recurrent alleles. Overall, 16.5% (50/304) of the tested patients carried 22 different pathogenic variants; 48% in BRCA1, 52% in BRCA2. Three variants, namely two in BRCA2 (Δexons 12 and 13 and c.7806-2A>T) and one in BRCA1 (c.5492del), constituting approximately half (48%) of all detected pathogenic variants, were shown to have a founder effect, with all carriers sharing common haplotypes. Remarkably, these variants were confined to Cretans and have not been identified in other regions of Greece. The high prevalence of specific BRCA1/2 pathogenic variants among Cretans, provides the possibility of cost- and time-efficient screening of the Cretan population. Integrating this knowledge in local public health services may have a significant impact on cancer prevention, and may serve as a starting point for the implementation of testing on a population level.

Prognostic impact of stromal and intratumoral CD3, CD8 and FOXP3 in adjuvantly treated breast cancer: do they add information over stromal tumor-infiltrating lymphocyte density?

BACKGROUND: Tumor-infiltrating lymphocytes (TILs) and their subsets contribute to breast cancer prognosis. We investigated the prognostic impact of CD3+, CD8+ and FOXP3+ TILs in patients with early intermediate/high-risk breast cancer treated with adjuvant anthracycline-based chemotherapy within two randomized trials conducted by our Group. METHODS: We examined 1011 patients (median follow-up 130.9 months) and their tumors for total, stromal (s) and intratumoral (i) CD3, CD8 and FOXP3 lymphocyte density (counts/mm2) on tissue-microarray cores by immunohistochemistry. Morphological sTIL density on whole H&E-stained sections was also evaluated. RESULTS: The majority of TILs were CD3+. Total CD3 and CD8, sCD3 and sCD8, iCD3 and iCD8, sFOXP3 and iFOXP3 were strongly correlated (Spearman's rho values > 0.6). High individual lymphocytic subsets and sTIL density were strongly associated with high tumor grade, higher proliferation and HER2-positive and triple-negative tumors (all p values < 0.001). Higher sTIL density (10% increments), high density of almost each individual marker and all-high profiles conferred favorable prognosis. However, when adjusted for sTIL density, stromal and intratumoral lymphocytic subsets lost their prognostic significance, while higher sTIL density conferred up to 15% lower risk for relapse. Independently of sTIL density, higher total CD3+ and CD8+ TILs conferred 35% and 28% lower risk for relapse, respectively. CONCLUSIONS: Stromal and intratumoral CD3+, CD8+ and FOXP3+ TIL density do not seem to add prognostic information over the morphologically assessed sTIL density, which is worth introducing in routine histology reports.

Clinical and psychometric features of psychiatric patients after a suicide attempt in relation with menstrual cycle phases.

There is evidence that frequency of suicide attempts of fertile women is related to the menstrual cycle phases, while the influence of hormonal and psychiatric features has been hypothesized. This study aims to explore the distribution and possible differences in clinical characteristics of women who attempted suicide in relation to menstrual cycle. Seventy fertile female psychiatric patients, hospitalized in psychiatric department after a suicide attempt, were studied. Depression was assessed using Beck Depression Inventory, suicide intent with the Suicide Intent Scale, and aggression using the Buss-Perry Aggression Questionnaire. A profile of psychopathology was obtained by using Symptom Check List SCL-90-R. Attempts were more frequent during the last 4 days of luteal phase and during the 4 days of menses, with 59% of attempts to occur during these 8 days. Patterns of number of attempts and cycle phase were similar for subgroups regarding diagnosis, violent/non-violent mode of suicide attempt, and one or repeated attempts. Although attempts were unequally distributed during the cycle, none of the psychiatric features assessed in the present study were related to the higher frequency of attempts during premenstrual/menstrual days, indicating the need to include additional aspects of suicidal behavior in future studies.

Patients' self-esteem before and after chemical peeling procedure.

INTRODUCTION: Chemical peeling is a safe method, widely used to treat a variety of skin conditions and reduce the aging effects. This study aims to evaluate self-esteem among adolescents who undergo chemical peelings. MATERIAL AND METHODS: One hundred and twenty six patients constituted the study group. Sixty seven individuals had undergone chemical peeling for therapeutic reasons and 59 individuals for cosmetic reasons. To assess patients' self-esteem, the Rosenberg's Self-esteem Scale (RSES) was used before and after treatment. The control group included 71 healthy, age- and sex-matched volunteers from the general population. They were also asked to complete the RSES, after the same time interval as the patients. RESULTS: The healthy controls (23.01 ± 3.12) presented statistically significantly higher self-esteem than both the groups of individuals who would be submitted to chemical peeling. Furthermore, patients who would undergo peeling for therapeutic reasons (21.58 ± 3.20) had statistically significantly higher self-esteem than those who would undergo the procedure for cosmetic reasons (18.97 ± 3.36). After the chemical peeling sessions, the self-esteem of patients treated for therapeutic reasons (23.48 ± 2.43) and of patients treated for cosmetic reasons (22.83 ± 3.34) improved statistically significantly, while the self-esteem of the healthy controls remained stable, as expected. CONCLUSION: Patients who undergo chemical peelings tend to have low levels of self-esteem. Although facial lesions in skin diseases such as acne, acne scars, rosacea, and melasma seem to have negative effect on individuals' self-consciousness, patients who would be submitted to chemical peeling in order to treat wrinkles, loss of radiance, and skin tone clarity have even lower self-esteem. Chemical peelings were shown to favorably affect patient's self-esteem since all patients showed an increase in self-esteem after treatment, while the control group experienced no change.

Psychotic (delusional) depression and completed suicide: a systematic review and meta-analysis.

BACKGROUND: It remains unclear whether psychotic features increase the risk of completed suicides in unipolar depression. The present systematic review coupled with a meta-analysis attempts to elucidate whether unipolar psychotic major depression (PMD) compared to non-PMD presents higher rates of suicides. METHODS: A systematic search was conducted in Scopus, PubMed, and "gray literature" for all studies providing data on completed suicides in PMD compared to non-PMD, and the findings were then subjected to meta-analysis. All articles were independently extracted by two authors using predefined data fields. RESULTS: Nine studies with 33,873 patients, among them 828 suicides, met our inclusion criteria. PMD compared to non-PMD presented a higher lifetime risk of completed suicides with fixed-effect pooled OR 1.21 (95% CI 1.04-1.40). In a sub-analysis excluding a very large study (weight = 86.62%), and comparing 681 PMD to 2106 non-PMD patients, an even higher pooled OR was found [fixed-effect OR 1.69 (95% CI 1.16-2.45)]. Our meta-analysis may provide evidence that the presence of psychosis increases the risk of suicide in patients suffering from severe depression. The data are inconclusive on the contribution of age, mood congruence, comorbidity, and suicide method on PMD's suicide risk. The lack of accurate diagnosis at the time of suicide, PMD's diagnostic instability, and the use of ICD-10 criteria constitute the main study limitations. CONCLUSIONS: The presence of psychosis in major depression should alert clinicians for the increased risk of completed suicide. Thus, the implementation of an effective treatment both for psychotic depression and patients' suicidality constitutes a supreme priority.

The Relationship between Hopelessness and Clinical Characteristics of Hospitalized Patients with Recent Suicide Attempt.

This study aimed to assess hopelessness in 170 hospitalized individuals with recent suicide attempt and examine its association with patients' characteristics, with a view to improving awareness in health professionals and especially nurses, who are among the first to take care of these patients. Participants completed Beck Hopelessness Scale and Beck Depression Inventory. More than half (51.18%) experienced moderate-to-severe hopelessness. A multiple linear regression analysis showed that age, attempted suicide method, past suicide attempt, and psychiatric diagnosis contributed statistically significantly to hopelessness prediction. Hopelessness assessment could efficiently help health professionals to minimize both inpatient suicide and suicidal acts after discharge.

Association of osteopontin with specific prognostic factors and survival in adjuvant breast cancer trials of the Hellenic Cooperative Oncology Group.

BACKGROUND: The shift towards an earlier diagnosis of breast cancer (BC) highlights the need for biomarkers that would identify patients at risk for relapse and metastatic spread and indicate the potential value of additional treatment strategies. Osteopontin (OPN) is a matricellular protein that has been suggested to be a potential biomarker in BC. In the present study, we used archived BC patient samples to assess the clinical utility of OPN. METHODS: Formalin-fixed paraffin-embedded tumor tissue samples from 975 patients were collected from two large phase III randomized adjuvant chemotherapy trials (HE10/97 and HE10/00) that included patients with high risk BC. All tissue samples were assessed for ER, PgR, Ki67 and HER2 protein expression. OPN protein and mRNA expression was evaluated using immunohistochemistry and quantitative reverse transcription-polymerase chain reaction, respectively. RESULTS: OPN mRNA expression data were available for 814 patients, whereas OPN protein expression data were available for 546 patients. The majority of patients were ER/PgR-positive (78.3%), HER2-negative (76.5%) and Ki67-positive (55.2%) and had received adjuvant radiation therapy (76.8%) and hormonal therapy (81.1%). OPN mRNA expression was significantly associated with age (60.9% in high OPN tumors vs. 54.1% in low OPN tumors, p = 0.047), ER/PgR-negative status (25.7 vs. 17.2%, p = 0.004) and BC subtypes (p = 0.021). In addition, high OPN mRNA expression was significantly associated with reduced DFS (HR 1.26, 95% CI 1.00-1.59, Wald's p = 0.050) and OS (HR 1.37, 95% CI 1.05-1.78, p = 0.019), while it retained its prognostic significance for both DFS (HR 1.39, 95% CI 1.10-1.77, p = 0.007) and OS (HR 1.54, 95% CI 1.61-2.05, p = 0.003) in the multivariate analysis. CONCLUSIONS: We showed that high OPN mRNA expression is associated with decreased DFS and OS in a large cohort of BC patients treated with adjuvant chemotherapy in a clinical trial setting. Our results suggest that OPN may serve as a prognostic factor and a potential target for therapy. Trial registration Australian New Zealand Clinical Trials Registry; HE10/97 ACTRN12611000506998; HE10/00 ACTRN12609001036202.

Lapatinib with whole brain radiotherapy in patients with brain metastases from breast and non-small cell lung cancer: a phase II study of the Hellenic Cooperative Oncology Group (HeCOG).

Small molecules, mainly tyrosine kinase inhibitors, are currently used in various malignancies. Lapatinib, a dual inhibitor of EGFR/HER2 tyrosine kinases, has demonstrated effectiveness in brain metastases from HER2-overexpressing breast cancer. It also appears to sensitize EGFR-expressing cell lines to radiation. To evaluate the efficacy of lapatinib in combination with whole brain radiotherapy (WBRT) in patients with brain metastases from non-small cell lung cancer (NSCLC) and breast cancer, as assessed by volumetric analysis by MRI. 81 patients were treated with WBRT (30 Gy in ten fractions) in combination with lapatinib 1250 mg once daily, followed by lapatinib 1500 mg once daily for a total 6 weeks. 21 patients had primary breast cancer and 60 patients NSCLC. Pre- and post-treatment MRI scans in a compact disk for central volumetric assessment were available for 43 patients. 27 patients (62.8%) achieved partial response, 15 patients (34.9%) had stable disease and only one patient (2.3%) had disease progression. Response was not associated to EGFR protein expression. All 81 patients were assessed for safety. The large majority of the adverse events were mild. Eight deaths occurred, four of which were considered related to the study drugs but there were also other contributing factors. Nine cases of serious infections were observed in eight patients, but they were also receiving dexamethasone. Lapatinib in combination with WBRT in patients with brain metastases from breast cancer and NSCLC is a feasible approach that can be further studied in larger clinical trials.

Expression and prognostic significance of VEGF and mTOR pathway proteins in metastatic renal cell carcinoma patients: a prognostic immunohistochemical profile for kidney cancer patients.

PURPOSE: To identify prognostic molecular profiles in patients with mRCC treated with sunitinib, we performed immunohistochemical analysis for VEGF and PI3K/Akt/mTOR pathway components. METHODS: The immunohistochemical expression of VEGF, p85α, p110γ, PTEN, p-Akt, p-mTOR, p-4E-BP1 and p-p70S6K was studied in 79 patients with mRCC who received first-line treatment with sunitinib. Expression was correlated with clinicopathological features and survival. RESULTS: VEGF was highly expressed (median H-Score 150), while positivity for the markers of the PI3K/Akt/mTOR pathway was: p85α 43/66 (65 %), p110γ41/60 (68 %), PTEN 32/64 (50 %), p-Akt57/63 (90 %), p-mTOR48/64 (75 %), p-4E-BP1 58/64 (90 %) and p-p70S6K 60/65 (92 %). No single immunohistochemical marker was found to have prognostic significance. Instead, the combination of increased p-mTOR and low VEGF expression was adversely correlated with overall survival (OS) (3.2 vs. 16.9 months, P = 0.001). CONCLUSION: Immunohistochemistry for VEGF and p-mTOR proteins may discriminate patients refractory to first-line sunitinib with poor prognosis. Prospective validation of our findings is needed.

Association of Plasma Cortisol Levels with Clinical Characteristics of Suicide Attempters.

OBJECTIVE: There is evidence that suicidal behavior, among others, is an abnormal response to stress caused by a dysfunction in the activity of hypothalamus-pituitary-adrenal axis, and that cortisol levels are low in a considerable number of people attempting suicide. In this study, we aimed to search for associations of plasma cortisol levels with the clinical characteristics of a group of psychiatric suicide attempters. METHOD: The cortisol was measured in the morning in 200 psychiatric patients hospitalized after a suicide attempt, with diagnoses of major depressive disorder, bipolar disorder, psychosis, and personality/adjustment disorder, and compared to the levels of 138 healthy controls. Comparisons were also made for diagnostic subgroups and across diagnoses, with regard to depressive symptomatology, mode of attempt, suicide intent, number of attempts, and age. RESULTS: Cortisol levels were significantly lower for the whole group of attempters compared to controls. Furthermore, low cortisol levels characterized attempters with personality/adjustment disorder, higher depressive symptomatology, low suicide intent, non-violent attempt mode, repeated attempts, and of younger age. CONCLUSIONS: Certain clinical characteristics were identified in attempters with low cortisol levels. In previous studies, low cortisol levels have been associated with impairments in cognitive control, decision-making, and emotional processing that may lead, in the presence of stressors, to suicidal behavior, frequently with non-fatal outcome. Adding plasma cortisol levels to demographic and psychopathological data may help in identifying a subpopulation of attempters with neurocognitive deficits linked to dysfunction of Hypothalamic-Pituitary-Adrenal-axis activity, with implications for treatment.

Body mass index and plasma leptin in psychiatric suicide attempters.

OBJECTIVES: To evaluate body mass index (BMI) and its correlate plasma leptin levels that have been associated with psychiatric morbidity and suicidal behaviour, in relation to clinical features in psychiatric patients after a suicide attempt. METHODS: BMI and plasma leptin were assessed in 198 patients (66 males, age range of 21 to 80 years) who were admitted to the hospital after a suicide attempt, 98 with major depressive disorder, 28 with bipolar disorder, 30 with psychosis, and 42 with personality or adjustment disorder, compared to data of 134 healthy subjects, and evaluated in relation to gender, diagnosis, mode of attempt, and pharmacological treatment before attempt. The ratio leptin/BMI was used as a measure of adipocyte leptin secreting activity. RESULTS: Drugs taken for treatment before attempt, among them atypical neuroleptics, were not associated either to BMI or to plasma leptin. The positive correlation between BMI and leptin was significant in all groups. Compared to same gender controls, significant differences were found only for female patients, namely higher BMI for patients with psychosis and patients with bipolar disorder, while leptin/BMI ratio was higher only in females with bipolar disorder. CONCLUSION: BMI and plasma leptin in psychiatric suicide attempters are elevated in certain diagnostic groups in females, not related to previous pharmacologic treatment. The lack of a control group without a history of suicide attempts does not allow the attribution of enhanced leptin secreting activity found in female bipolar attempters specifically to suicidal behavior or to the disorder as a diagnostic entity.

Comparative study of hostility in depressive patients with and without a suicide attempt history.

Hostility in association with depression seems to be connected to suicidal behavior. This study aimed to evaluate hostility and its dimensions in relation to depression in patients who suffered from diagnosed depression with and without a suicide attempt history. The study included 168 participants; 58 patients with depression and suicide attempt history, 55 patients with depression without a suicide attempt history and 55 healthy controls. Hostility was assessed with the Hostility and Direction of Hostility Questionnaire, while depression with the Beck Depression Inventory (BDI). Patients with depression and a suicide attempt history compared with the patients without attempt history presented statistically significantly higher total hostility (28.71 ± 6.43 vs 24.20 ± 7.66), extroverted hostility (17.16 ± 4.37 vs 14.15 ± 4.63), acting out hostility (6.03 ± 2.09 vs 4.73 ± 1.93), and self criticism (6.95 ± 2.12 vs 5.89 ± 2.32). No statistically significant differences were found between the two clinical groups in depression according to the BDI. Moreover depressive patients with suicide attempt history scored higher in all the hostility dimensions than the controls. Therefore, it could be suggested that hostility and especially its extrapunitive dimensions are associated with suicidal behavior, since no differences in depression were recorded between the two clinical groups.

A case-control study of hopelessness and suicidal behavior in the city of Athens, Greece. The role of the financial crisis.

This study aimed to examine the psychometric properties of Beck Hopelessness Scale (BHS) in Greek patients with a recent suicide attempt, the predictive ability of BHS especially in terms of age and the possible effect of the financial crisis on hopelessness as it has been identified as a significant suicide risk factor. The study included a total of 510 individuals, citizens of Athens, Greece. Three hundred and forty individuals (170 attempted suicide patients, and 170 -age and gender- matched healthy individuals used as controls) completed BHS before the financial crisis onset (from 2009 to 2010). A sample of 170 healthy individuals also completed the BHS after the financial crisis onset (from 2013 to 2014), when the impact of the austerity measures was being felt by the Greek society. The Greek BHS version demonstrated good psychometric properties and a sufficient degree of internal consistency. Attempted suicide patients (M = 9) presented higher hopelessness than the controls (M = 3). The patients' age positively correlated with hopelessness (rs = .35, p < .001), and the ROC curve revealed that the BHS ability to discriminate the individuals with pathological rates of hopelessness from those without, strengthened as age increased. No significant differences were found between the individuals evaluated before (M = 3) and after (M = 3, p > .05) the crisis onset. Nevertheless, regarding the latter group, the women, the younger individuals, the less educated, the unemployed and the participants with low or mediocre self-reported financial status presented increased hopelessness. Our findings suggest that BHS could be a useful instrument especially when screening for suicide risk in people of older age, and that the financial crisis in Greece had a greater impact on subgroups of the population regarding hopelessness.

Effects of TP53 and PIK3CA mutations in early breast cancer: a matter of co-mutation and tumor-infiltrating lymphocytes.

The purpose of this study is to investigate whether the outcome of breast cancer (BC) patients treated with adjuvant chemotherapy is affected by co-mutated TP53 and PIK3CA according to stromal tumor-infiltrating lymphocytes (TILs). Paraffin tumors of all clinical subtypes from 1661 patients with operable breast cancer who were treated within 4 adjuvant trials with anthracycline-taxanes chemotherapy were informative for TP53 and PIK3CA mutation status (semiconductor sequencing genotyping) and for stromal TILs density. Disease-free survival (DFS) was examined. TP53 mutations were associated with higher (p < 0.001) and PIK3CA with lower (p = 0.004) TILs in an ER /PgR-specific manner (p < 0.001). Mutations did not affect the favorable DFS of patients with lymphocyte-predominant (LP) BC. Within non-LPBC, PIK3CA-only mutations conferred best, while TP53-PIK3CA co-mutations (6 % of all tumors) conferred worst DFS (HR 0.59; 95 % CI 0.44-0.79; p = 0.001 for PIK3CA-only). TP53-only mutations were unfavorable in patients with lower TILs, while patients with lower TILs performed worse if their tumors carried TP53-only mutations (interaction p = 0.046). Multivariate analysis revealed favorable PIK3CA-only mutations in non-LPBC (HR 0.64; 95 % CI 0.47-0.88; p = 0.007), and unfavorable TP53 mutations in ER/PgRpos/HER2neg (HR 1.55; 95 % CI 1.07-2.24; p = 0.021). Mutations did not interact with TILs in non-LP triple-negative and HER2-positive patients. TP53 and PIK3CA mutations appear to have diverse effects on the outcome of early BC patients, according to whether these genes are co-mutated or not, and for TP53 according to TILs density and ER/PgR-status. These findings need to be considered when evaluating the effect of these two most frequently mutated genes in the context of large clinical trials.

MYC copy gain, chromosomal instability and PI3K activation as potential markers of unfavourable outcome in trastuzumab-treated patients with metastatic breast cancer.

BACKGROUND: There is an unmet need for more efficient patient stratification for receiving trastuzumab in the metastatic breast cancer (mBC) setting, since only part of such patients benefit from the addition of this agent to chemotherapy. The aim of this study was to investigate the prognostic value of biomarkers including MYC and MET in mBC patients treated with trastuzumab-based regimens. METHODS: mBC patients, locally tested as HER2-positive, treated with trastuzumab and chemotherapy between 1998 and 2010 were evaluated. Paraffin tumors (n = 229) were retrospectively centrally assessed by immunohistochemistry (IHC) for HER2, ER, PgR and Ki67; fluorescence in situ hybridization (FISH) for HER2, TOP2A and centromere (CEN) 17, MYC and CEN8, MET and CEN7; qPCR for MYC, MET copy number (CN); and, for PI3K activation (PIK3CA mutations; PTEN and phospho-mTOR protein expression). Increased CEN CN was assessed based on normal cut-offs. Time to progression (TTP) and survival were evaluated from the initiation of trastuzumab as first line treatment. RESULTS: Among all tumors, 90 were HER2-negative upon central testing (ambiguous HER2) and the rest were true HER2-positive. Further, 156 patients presented with mBC upon relapse of pre-treated disease (R-mBC) and 65 were diagnosed at stage IV (de novo mBC). Concordance between FISH and qPCR on gene CN status was fair for MYC (Kappa = 0.458) and absent for MET. The presence of MYC CN gain with qPCR and the absence of PI3K activation were infrequent events (7 and 8 % of evaluable tumors, respectively), while 41 % of tumors had increased CEN CN in one or more chromosomes, indicative of chromosomal instability. The most consistent finding in the entire cohort and in the above patient subgroups with respect to outcome was the unfavourable effect of MYC CN gain, which was retained upon multivariable analysis (e.g., survival in the entire cohort, HR 6.02; 95 % CI 2.67-13.6; p < 0.001). Further unfavourable prognosticators were increased CEN CN in one chromosome in R-mBC but not in de novo mBC (multivariable interaction p = 0.048), PI3K activation in R-mBC (multivariable p = 0.004) and increased Ki67 for patient TTP. CONCLUSIONS: MYC gene copies, centromere status and PI3K activation may adversely impact trastuzumab treated mBC patient outcome and seem worthy validating in larger series.

Monolayer Phases of a Dipolar Perylene Derivative on Au(111) and Surface Potential Build-Up in Multilayers.

9-(Bis-p-tert-octylphenyl)-amino-perylene-3,4-dicarboxy anhydride (BOPA-PDCA) is a strongly dipolar molecule representing a group of asymmetrically substituted perylenes that are employed in dye-sensitized solar cells and hold great promise for discotic liquid crystal applications. Thin BOPA-PDCA films with orientated dipole moments can potentially be used to tune the energy-level alignment in electronic devices and store information. To help assessing these prospects, we here elucidate the molecular self-assembly and electronic structure of BOPA-PCDA employing room temperature scanning tunneling microscopy and spectroscopy in combination with ultraviolet and X-ray photoelectron spectroscopies. BOPA-PCDA monolayers on Au(111) exclusively form in-plane antiferroelectric phases. The molecular arrangements, the increase of the average number of molecules per unit cell via ripening, and the rearrangement upon manipulation with the STM tip indicate an influence of the dipole moment on the molecular assembly and the rearrangement. A slightly preferred out-of-plane orientation of the molecules in the multilayer induces a surface potential of 1.2 eV. This resembles the giant surface potential effect that was reported for vacuum-deposited tris(8-hydroxyquinoline)aluminum and deemed applicable for data storage. Notably, the surface potential in the case of BOPA-PDCA can in part be reversibly removed by visible light irradiation.

Two cycles of adjuvant carboplatin in stage I seminoma: 8-year experience by the Hellenic Cooperative Oncology Group (HECOG).

PURPOSE: Following the establishment of adjuvant carboplatin in stage I testicular seminoma as a standard, we adopted this treatment for all stage I seminoma patients. We report our 8-year experience and compare these results with our previous adjuvant etoposide/cisplatin (EP) strategy. PATIENTS AND METHODS: Patients with stage I seminoma, treated with adjuvant carboplatin and with a minimum follow-up of 1 year, were included. Two cycles of carboplatin [area under the curve (AUC) 6] were administered. RESULTS: A total of 138 patients with median age of 34 years, treated from September 2003 to December 2011, were selected. There were 5 relapses [5-year relapse-free rate (RFR) 96.8 % (95 % confidence interval 91.6-98.8)]: 3 relapses at retroperitoneal lymph nodes, 1 relapse at the adrenal gland, and 1 isolated brain metastasis. Four patients with relapse were cured with salvage chemotherapy. All patients with relapse had tumor diameter ≥4 cm and/or age ≤34 years. Patients with at least 1 of the above risk factors (n = 111) had a significantly higher relapse rate compared with a similar population (n = 64) treated with 2 cycles of adjuvant EP: 5-year RFR was 95 % (SE 2 %) versus 100 % (SE 0 %), (p = 0.067). CONCLUSIONS: Age and tumor diameter were associated with relapse in stage I seminoma treated with adjuvant carboplatin. Although adjuvant carboplatin in patients with age ≤34 and/or tumor diameter ≥4 cm is associated with higher relapse rates than EP, the prognosis of these patients is excellent, and therefore, the use of less toxic treatment is justified.

Comparative study of quality of life and psychosocial characteristics in patients with psoriasis and leg ulcers.

Psoriasis and leg ulcers have a marked impact on the patient's quality of life and represent a life-long burden for affected patients. The aim of this study is to compare the quality of life, anxiety and depression, self-esteem, and loneliness in patients with psoriasis and leg-ulcer patients. Eighty patients with leg ulcers, eighty patients with psoriasis, and eighty healthy controls were included in this study. The quality of life, depression and anxiety, loneliness of the patient, and self-esteem were assessed using the Dermatology Life Quality Index (DLQI), Hospital Anxiety and Depression Scale (HADS), the UCLA loneliness Scale (UCLA-Version 3), and the Rosenberg's Self-esteem Scale (RSES), respectively. The DLQI score among patients with psoriasis was 12.74 ± 4.89 and leg ulcer patients was 13.28 ± 2.57. The patients with psoriasis presented statistically significant higher anxiety (9.87 ± 4.56) than both leg ulcer patients (8.26 ± 2.82) and controls (6.45 ± 1.89), while leg ulcer patients also presented higher anxiety than controls. Regarding self-esteem, although there were no significant differences between the patients with psoriasis (15.25 ± 3.20) and the ones with leg ulcers (15.89 ± 2.93), they both presented statistically significant lower self-esteem scores than control group (18.53 ± 3.04). The patients with psoriasis presented statistically significant higher levels of loneliness and social isolation (46.18 ± 6.63) compared to leg ulcer patients (43.73 ± 5.68) than controls (42.49 ± 3.41). Psoriasis and leg ulcers are long-term skin diseases associated with significant impairment of the patient's quality of life, anxiety, and self-esteem, which are frequently under-recognized.

Quality of Life and Psychosocial Implications in Patients with Hidradenitis Suppurativa.

BACKGROUND: Hidradenitis suppurativa (HS) is a long-term skin disorder associated with high levels of psychological distress and significant life impact. OBJECTIVE: To evaluate the quality of life, depression, anxiety, loneliness, and self-esteem in patients with HS. METHODS: Ninety-four patients with HS were enrolled in the study. The quality of life, depression, anxiety, loneliness, and self-esteem of the patients were assessed using the Dermatology Life Quality Index (DLQI), the Hospital Anxiety and Depression Scale (HADS), the UCLA Loneliness Scale (UCLA-Version 3), and the Rosenberg Self-Esteem Scale (RSES), respectively. RESULTS: The DLQI mean score was 11.43 ± 6.61 in patients with HS. The patients with HS presented statistically significantly higher anxiety (6.41 ± 3.31 vs. 5.00 ± 1.59, p < 0.001), depression (5.45 ± 2.79 vs. 4.16 ± 1.54, p < 0.001), and loneliness and social isolation scores (42.86 ± 8.63 vs. 35.57 ± 6.17, p < 0.001) and lower self-esteem scores (18.91 ± 1.79 vs. 19.77 ± 2.53, p = 0.008) than the healthy controls. CONCLUSIONS: HS is a distressing, recurrent disease that impairs quality of life. We can suggest services that allow an integrated approach, which includes psychosocial support, offering the patients relief from isolation and an opportunity to share common experiences.