MMP-9 as predictive factor for response and progression free survival in breast cancer patients treated with bevacizumab and pegylated liposomal doxorubicin. A multicenter, single-arm phase II trial (SAKK24/06). On behalf of the Swiss Group for Clinical Cancer Research (SAKK).

The benefit of bevacizumab (Bv) has been shown in different tumors including colorectal cancer, renal cancer, pulmonary non-small cell cancer and also breast cancer. However to date, there is no established test evaluating the angiogenic status of a patient and monitoring the effects of anti-angiogenic treatments. Tumor angiogenesis is the result of a balance between multiple pro- and anti¬angiogenic molecules. There is very little published clinical data exploring the impact of the anti-angiogenic therapy on the different angiogenesis-related molecules and the potential role of these molecules as prognostic or predictive factors.

Continuous Sunitinib treatment in patients with advanced hepatocellular carcinoma: a Swiss Group for Clinical Cancer Research (SAKK) and Swiss Association for the Study of the Liver (SASL) multicenter phase II trial (SAKK 77/06).

BACKGROUND: Sunitinib (SU) is a multitargeted tyrosine kinase inhibitor with antitumor and antiangiogenic activity. The objective of this trial was to demonstrate antitumor activity of continuous SU treatment in patients with hepatocellular carcinoma (HCC). PATIENTS AND METHODS: Key eligibility criteria included unresectable or metastatic HCC, no prior systemic anticancer treatment, measurable disease, and Child-Pugh class A or mild Child-Pugh class B liver dysfunction. Patients received 37.5 mg SU daily until progression or unacceptable toxicity. The primary endpoint was progression-free survival at 12 weeks (PFS12). RESULTS: Forty-five patients were enrolled. The median age was 63 years; 89% had Child-Pugh class A disease and 47% had distant metastases. PFS12 was rated successful in 15 patients (33%; 95% confidence interval, 20%-47%). Over the whole trial period, one complete response and a 40% rate of stable disease as the best response were achieved. The median PFS duration, disease stabilization duration, time to progression, and overall survival time were 1.5, 2.9, 1.5, and 9.3 months, respectively. Grade 3 and 4 adverse events were infrequent. None of the 33 deaths were considered drug related. CONCLUSION: Continuous SU treatment with 37.5 mg daily is feasible and has moderate activity in patients with advanced HCC and mild to moderately impaired liver dysfunction. Under this trial design (>13 PFS12 successes), the therapy is considered promising. This is the first trial describing the clinical effects of continuous dosing of SU in HCC patients on a schedule that is used in an ongoing, randomized, phase III trial in comparison with the current treatment standard, sorafenib (ClinicalTrials.gov identifier, NCT00699374).

International Society of Urological Pathology (ISUP) Consensus Conference on Handling and Staging of Radical Prostatectomy Specimens. Working group 5: surgical margins.

The 2009 International Society of Urological Pathology Consensus Conference in Boston, made recommendations regarding the standardization of pathology reporting of radical prostatectomy specimens. Issues relating to surgical margin assessment were coordinated by working group 5. Pathologists agreed that tumor extending close to the 'capsular' margin, yet not to it, should be reported as a negative margin, and that locations of positive margins should be indicated as either posterior, posterolateral, lateral, anterior at the prostatic apex, mid-prostate or base. Other items of consensus included specifying the extent of any positive margin as millimeters of involvement; tumor in skeletal muscle at the apical perpendicular margin section, in the absence of accompanying benign glands, to be considered organ confined; and that proximal and distal margins be uniformly referred to as bladder neck and prostatic apex, respectively. Grading of tumor at positive margins was to be left to the discretion of the reporting pathologists. There was no consensus as to how the surgical margin should be regarded when tumor is present at the inked edge of the tissue, in the absence of transected benign glands at the apical margin. Pathologists also did not achieve agreement on the reporting approach to benign prostatic glands at an inked surgical margin in which no carcinoma is present.

Induction of circulating tumor-reactive CD8+ T cells after vaccination of melanoma patients with the gp100 209-2M peptide.

Patients with stage I-III melanoma were vaccinated with the modified HLA-A2-binding gp100(209-2M)-peptide after complete surgical resection of their primary lesion and sentinel node biopsy. Cytoplasmic interferon-gamma production by freshly thawed peripheral blood mononuclear cells (direct ex vivo analysis) or by peripheral blood mononuclear cells subjected to 1 cycle of in vitro sensitization with peptide, interleukin-2, and interleukin-15 was measured following restimulation with the modified and native gp100 peptides, and also A2gp100 melanoma cell lines. Peptide-reactive and tumor-reactive T cells were detected in 79% and 66% of selected patients, respectively. Patients could be classified into 3 groups according to their vaccine-elicited T-cell responses. One group of patients responded only to the modified peptide used for immunization, whereas another group of patients reacted to both the modified and native gp100 peptides, but not to naturally processed gp100 antigen on melanoma cells. In the third group of patients, circulating CD8 T cells recognized A2gp100 melanoma cell lines and also both the modified and native peptides. T cells with a low functional avidity, which were capable of lysing tumor cells only if tumor cells were first pulsed by the exogenous administration of native gp100(209-217) peptide were identified in most patients. These results indicate that vaccination with a modified gp100 peptide induced a heterogeneous group of gp100-specific T cells with a spectrum of functional avidities; however, high avidity, tumor-reactive T cells were detected in the majority of patients.

Social mobility in 20th century, Switzerland

The study of social mobility enables us to assess the extent to which a given society is "open". Addressing this issue is particularly crucial in our democratic societies, where it is expected that the place of individuals in society should no longer be determined at birth, but rather by individual quality. The present inquiry investigates this issue in the context of Switzerland, a country characterised by specific institutional settings, notably through the close association its educational system shares with the labour market. Through a detailed empirical analysis based on robust statistical analyses carried out from a unique tailor-made dataset, I demonstrate that Swiss society has not become more open throughout the twentieth century. Although some barriers have lost some salience, Swiss society has overall remained extremely rigid. In particular, because it channels individuals into highly segmented tracks very early on, the Swiss educational system does not attenuate social background differences. Thus, Switzerland is found in a particular configuration where an individual's place in society is highly determined not only by his or her educational attainment, but also by his or her social background. In other words, Switzerland constitutes a sort of "non-meritocratic meritocracy". - L'étude de la mobilité sociale permet d'évaluer dans quelle mesure une société donnée est « ouverte ». S'intéresser à cette question est particulièrement crucial dans nos sociétés démocratiques, où il est attendu que la place des individus ne soit plus déterminée à la naissance, mais plutôt par les qualités individuelles. La présente étude examine cette question dans le cadre de la Suisse, un pays aux caractéristiques institutionnelles spécifiques, particulièrement de part le lien étroit que son système éducatif entretien avec le marché du travail. A travers une analyse empirique détaillée fondée sur des analyses statistiques robustes menées à partir d'un jeu de données unique construit sur-mesure, je démontre que la société suisse n'est pas devenue plus ouverte au cours du 20ème siècle. Même si certaines barrières ont perdu de l'importance, dans son ensemble, la société suisse est restée extrêmement rigide. En particulier, parce qu'il oriente très tôt les individus dans des filières fortement segmentées, le système éducatif suisse n'atténue pas les différences entre milieux sociaux. Ainsi, la Suisse se trouve dans une configuration particulière où, d'une part, la place d'un individu dans la société est hautement déterminée par son niveau d'étude et, d'autre part, par son origine sociale. En d'autres termes, la Suisse apparaît comme une sorte de « méritocratie non-méritocratique ».

Attenuated poxviruses expressing a synthetic HIV protein stimulate HLA-A2-restricted cytotoxic T-cell responses.

Efficient HIV vaccines have to trigger cell-mediated immunity directed against various viral antigens. However little is known about the breadth of the response induced by vaccines carrying multiple proteins. Here, we report on the immunogenicity of a construct harbouring a fusion of the HIV-1 IIIB gag, pol and nef genes (gpn) designed for optimal safety and equimolar expression of the HIV proteins. The attenuated poxviruses, MVA and NYVAC, harbouring the gpn construct, induced potent immune responses in conventional mice characterised by stimulation of Gpn-specific IFN-gamma-producing cells and cytotoxic T cells. In HLA-A2 transgenic mice, recombinant MVA elicited cytotoxic responses against epitopes recognised in most HLA-A2+ HIV-1-infected individuals. We also found that the MVA vaccine triggered the in vitro expansion of peripheral blood cells isolated from a HIV-1-seropositive patient and with similar specificity as found in immunised HLA-A2 transgenic mice. In conclusion, the synthetic HIV polyantigen Gpn delivered by MVA is immunogenic, efficiently processed and presented by human MHC class I molecules.

Treatment of localised resectable neuroblastoma. Results of the LNESG1 study by the SIOP Europe Neuroblastoma Group.

Main objective of this study was to confirm that surgery alone is an effective and safe treatment for localised resectable neuroblastoma except stage 2 with amplified MYCN gene (MYCNA). Of 427 eligible stages 1-2 patients, 411 had normal MYCN and 16 had MYCNA. Of the 288 stage 1 patients with normal MYCN, 1 died of complications and 16 relapsed, 2 of whom died; 5-year relapse-free survival (RFS) and overall survival (OS) rates were 94.3% (95% confidence interval (CI): 91.6-97) and 98.9% (95% CI: 97.7-100), respectively. Of the 123 stage 2 patients with normal MYCN, 1 died of sepsis and 22 relapsed, 8 of whom died (RFS 82.8%, 95% CI: 76.2-89.5; OS 93.2%, 95% CI: 88.7-97.8). In stage 2, OS and RFS were worse for patients with elevated LDH and unfavourable histopathology. Of 16 children with MYCNA, 7 were stage 1 (5 relapses and 4 deaths) and 9 were stage 2 (3 relapses and 2 deaths) patients. In conclusion, surgery alone yielded excellent OS for both stage 1 and 2 neuroblastoma without MYCNA, although stage 2 patients with unfavourable histopathology and elevated LDH suffered a high number of relapses. Both stage 1 and 2 patients with MYCNA were at greater risk of relapse.

International Society of Urological Pathology (ISUP) Consensus Conference on Handling and Staging of Radical Prostatectomy Specimens. Working group 3: extraprostatic extension, lymphovascular invasion and locally advanced disease.

The International Society of Urological Pathology Consensus Conference on Handling and Staging of Radical Prostatectomy Specimens in Boston made recommendations regarding the standardization of pathology reporting of radical prostatectomy specimens. Issues relating to extraprostatic extension (pT3a disease), bladder neck invasion, lymphovascular invasion and the definition of pT4 were coordinated by working group 3. It was agreed that prostate cancer can be categorized as pT3a in the absence of adipose tissue involvement when cancer bulges beyond the contour of the gland or beyond the condensed smooth muscle of the prostate at posterior and posterolateral sites. Extraprostatic extension can also be identified anteriorly. It was agreed that the location of extraprostatic extension should be reported. Although there was consensus that the amount of extraprostatic extension should be quantitated, there was no agreement as to which method of quantitation should be employed. There was overwhelming consensus that microscopic urinary bladder neck invasion by carcinoma should be reported as stage pT3a and that lymphovascular invasion by carcinoma should be reported. It is recommended that these elements are considered in the development of practice guidelines and in the daily practice of urological surgical pathology.

Theory of mind tasks and executive functions: A systematic review of group studies in neurology.

A growing number of studies have been addressing the relationship between theory of mind (TOM) and executive functions (EF) in patients with acquired neurological pathology. In order to provide a global overview on the main findings, we conducted a systematic review on group studies where we aimed to (1) evaluate the patterns of impaired and preserved abilities of both TOM and EF in groups of patients with acquired neurological pathology and (2) investigate the existence of particular relations between different EF domains and TOM tasks. The search was conducted in Pubmed/Medline. A total of 24 articles met the inclusion criteria. We considered for analysis classical clinically accepted TOM tasks (first- and second-order false belief stories, the Faux Pas test, Happe's stories, the Mind in the Eyes task, and Cartoon's tasks) and EF domains (updating, shifting, inhibition, and access). The review suggests that (1) EF and TOM appear tightly associated. However, the few dissociations observed suggest they cannot be reduced to a single function; (2) no executive subprocess could be specifically associated with TOM performances; (3) the first-order false belief task and the Happe's story task seem to be less sensitive to neurological pathologies and less associated to EF. Even though the analysis of the reviewed studies demonstrates a close relationship between TOM and EF in patients with acquired neurological pathology, the nature of this relationship must be further investigated. Studies investigating ecological consequences of TOM and EF deficits, and intervention researches may bring further contributions to this question.

Subjective Memory Deficits in People with and without Dementia: Findings from the 10/66 Dementia Research Group Pilot Studies in Low- and Middle-Income Countries

OBJECTIVES To compare subjective memory deficit (SMD) in older adults with and without dementia or depression across multiple centers in low- and middle-income countries (LAMICs). DESIGN Secondary analysis of data from 23 case control studies. SETTING Twenty-three centers in India, Southeast Asia (including China), Latin America and the Caribbean, Nigeria, and Russia. PARTICIPANTS Two thousand six hundred ninety-two community-dwelling people aged 60 and older in one of three groups: people with dementia, people with depression, and controls free of dementia and depression. MEASUREMENTS SMD was derived from the Geriatric Mental State examination. RESULTS Median SMD frequency was lowest in participants without dementia (26.2%) and higher in those with depression (50.0%) and dementia (66.7%). Frequency of SMD varied between centers. Depression and dementia were consistently associated with SMD. Older age and hypochondriasis were associated with SMD only in subjects without dementia. In those with dementia, SMD was associated with better cognitive function, whereas the reverse was the case in controls. CONCLUSION Associations with SMD may differ between subjects with and without dementia living in LAMICs.

Outcome of long-axis percutaneous sacroplasty as first-line treatment of sacral insufficiency fractures : P219

Purpose: To assess the clinical outcome of patients who were subjected to long-axis sacroplasty as first line treatment for sacral insufficiency fractures. Methods and materials: Nineteen patients with unilateral (n = 3) or bilateral (n = 16) sacral fractures were involved. Under local anaesthesia, each patient was subjected to CT guided sacroplasty using the long-axis approach through a single entry point. An average of 6 ml of PMMA was delivered along the path of each sacral fracture. For each individual patient, the VAS pain score before sacroplasty and at 1, 4, 24, and 48 weeks after the procedure was obtained. Furthermore, the use of analgesics (narcotic/non-narcotic) along with the evolution of post interventional patient mobility before and after sacroplasty was also recorded. Results: The mean pre-procedure VAS score was 8 ± 1.9. This has rapidly declined in the first week after the procedure (mean 4 ± 1.5) followed by gradual decrease along the rest of follow-up period at 4 weeks (mean 3 ± 1.2), 24 weeks (mean 2 ± 1.3), and 48 weeks (mean 1.3 ± 1.4), respectively. Eleven (58%) patients were under narcotic analgesia before sacroplasty, whereas, 8 (42%) patients were using non-narcotics. Corresponding values after the procedure were 2/19 (10%) (narcotic) and 10/19 53% (non-narcotic). Seven (37%) patients did not address post-procedure analgesic use. The evolution of post interventional mobility was favourable in the study group since they revealed a significant improvement in their mobility point scale. Conclusion: Long-axis percutaneous sacroplasty is a suitable minimally invasive treatment option for patients who present with sacral insufficiency fractures. Future studies with larger patient number are warranted to grasp any potential limitations of this therapeutic approach.

Protein intake and exercise for optimal muscle function with aging: recommendations from the ESPEN Expert Group.

The aging process is associated with gradual and progressive loss of muscle mass along with lowered strength and physical endurance. This condition, sarcopenia, has been widely observed with aging in sedentary adults. Regular aerobic and resistance exercise programs have been shown to counteract most aspects of sarcopenia. In addition, good nutrition, especially adequate protein and energy intake, can help limit and treat age-related declines in muscle mass, strength, and functional abilities. Protein nutrition in combination with exercise is considered optimal for maintaining muscle function. With the goal of providing recommendations for health care professionals to help older adults sustain muscle strength and function into older age, the European Society for Clinical Nutrition and Metabolism (ESPEN) hosted a Workshop on Protein Requirements in the Elderly, held in Dubrovnik on November 24 and 25, 2013. Based on the evidence presented and discussed, the following recommendations are made (a) for healthy older people, the diet should provide at least 1.0-1.2 g protein/kg body weight/day, (b) for older people who are malnourished or at risk of malnutrition because they have acute or chronic illness, the diet should provide 1.2-1.5 g protein/kg body weight/day, with even higher intake for individuals with severe illness or injury, and (c) daily physical activity or exercise (resistance training, aerobic exercise) should be undertaken by all older people, for as long as possible.

Docetaxel, cisplatin, and fluorouracil; docetaxel and cisplatin; and epirubicin, cisplatin, and fluorouracil as systemic treatment for advanced gastric carcinoma: a randomized phase II trial of the Swiss Group for Clinical Cancer Research.

PURPOSE: This randomized phase II trial evaluated two docetaxel-based regimens to see which would be most promising according to overall response rate (ORR) for comparison in a phase III trial with epirubicin-cisplatin-fluorouracil (ECF) as first-line advanced gastric cancer therapy. PATIENTS AND METHODS: Chemotherapy-naïve patients with measurable unresectable and/or metastatic gastric carcinoma, a performance status <or= 1, and adequate hematologic, hepatic, and renal function randomly received <or= eight 3-weekly cycles of ECF (epirubicin 50 mg/m(2) on day 1, cisplatin 60 mg/m(2) on day 1, and fluorouracil [FU] 200 mg/m(2)/d on days 1 to 21), TC (docetaxel initially 85 mg/m(2) on day 1 [later reduced to 75 mg/m(2) as a result of toxicity] and cisplatin 75 mg/m(2) on day 1), or TCF (TC plus FU 300 mg/m(2)/d on days 1 to 14). Study objectives included response (primary), survival, toxicity, and quality of life (QOL). RESULTS: ORR was 25.0% (95% CI, 13% to 41%) for ECF, 18.5% (95% CI, 9% to 34%) for TC, and 36.6% (95% CI, 23% to 53%) for TCF (n = 119). Median overall survival times were 8.3, 11.0, and 10.4 months for ECF, TC, and TCF, respectively. Toxicity was acceptable, with one toxic death (TC arm). Grade 3 or 4 neutropenia occurred in more treatment cycles with docetaxel (TC, 49%; TCF, 57%; ECF, 34%). Global health status/QOL substantially improved with ECF and remained similar to baseline with both docetaxel regimens. CONCLUSION: Time to response and ORR favor TCF over TC for further evaluation, particularly in the neoadjuvant setting. A trend towards increased myelosuppression and infectious complications with TCF versus TC or ECF was observed.

Strategies to promote translational research within the European Organisation for Research and Treatment of Cancer (EORTC) Head and Neck Cancer Group: a report from the Translational Research Subcommittee.

Head and neck squamous cell cancer (HNSCC) is the sixth leading cause of cancer-related deaths worldwide. These tumors are commonly diagnosed at advanced stages and mortality rates remain high. Even cured patients suffer the consequences of aggressive treatment that includes surgery, chemotherapy, and radiotherapy. In the past, in clinical trials, HNSCC was considered as a single disease entity. Advances in molecular biology with the development of genomic and proteomic approaches have demonstrated distinct prognostic HNSCC patient subsets beyond those defined by traditional clinical-pathological factors such as tumor subsite and stage [Cho W (ed). An Omics Perspective on Cancer Research. New York/Berlin: Springer 2010]. Validation of these biomarkers in large prospective clinical trials is required before their clinical implementation. To promote this research, the European Organisation for Research and Treatment of Cancer (EORTC) Head and Neck Cancer Program will develop the following strategies-(i) biobanking: prospective tissue collection from uniformly treated patients in the setting of clinical trials; (ii) a group of physicians, physician-scientists, and EORTC Headquarters staff devoted to patient-oriented head and neck cancer research; (iii) a collaboration between the basic scientists of the Translational Research Division interested in head and neck cancer research and the physicians of the Head and Neck Cancer Group; and (iv) funding through the EORTC Grant Program and the Network Core Institutions Consortium. In the present report, we summarize our strategic plans to promote head and neck cancer research within the EORTC framework.