Self-changing behaviour in smoking cessation linked to trait and cognitive impulsivity.

BACKGROUND AND AIMS: To compare impulsivity, measured using self-report and cognitive tasks in people who ceased smoking without treatment (self-changers) with each of the following groups: (i) smoking non-treatment-seekers, (ii) people in smoking cessation treatment and currently abstinent and (iii) people in smoking cessation treatment but non-abstinent. DESIGN: Cross-sectional, observational study. SETTING: The smoking cessation unit of a public general hospital, Hospital de Santa Maria, in Lleida, Spain. All participants were from the hospital's catchment area. PARTICIPANTS: One hundred and twenty participants, classified in four groups: (1) self-changers (n = 30, 21 females, mean age = 41.50 years), (2) non-treatment-seekers (n = 30, 17 females, mean age = 35.27 years), (3) people in smoking cessation treatment and currently abstinent (n = 30, 17 females, mean age = 48.93 years) and (4) people in smoking cessation treatment but non-abstinent (n = 30, 21 females, mean age = 33.70 years). MEASUREMENTS: The Barratt Impulsiveness Scale, including measures of non-planning, attentional and motor impulsivity, and two behavioural tasks measuring cognitive inhibition (Stroop test) and choice impulsivity (delay-discounting task). Confounders included sex, age, education, employment, smoking severity, depression and trait and state anxiety. FINDINGS: Although not on the other three measures, we found significant group differences on trait non-planning impulsivity and Stroop performance. Self-changers, compared with non-treatment-seekers, had lower non-planning impulsivity (P = 0.018, Cohen's d = 0.62) and better Stroop performance (P = 0.001, Cohen's d = 0.66). Self-changers also had better Stroop performance than participants in treatment and currently abstinent (P = 0.002, Cohen's d = 0.85). CONCLUSIONS: People who have stopped smoking without treatment appear to have lower non-planning impulsivity and more effective cognitive inhibition compared with smoking non-treatment-seekers, and better cognitive inhibition than people who cease smoking with treatment aid.

Phase I study of sunitinib in combination with gemcitabine and capecitabine for first-line treatment of metastatic or unresectable renal cell carcinoma.

BACKGROUND: The combination of gemcitabine plus capecitabine and sunitinib (GCS) shows activity in metastatic renal cell carcinoma (mRCC). We tested the multitargeted "chemo-switch" regimen as first-line treatment in patients with mRCC. METHODS: We assessed the maximum tolerated dose and antitumor activity of GCS in treatment-naïve, advanced mRCC patients. Treatment consisted of intravenous gemcitabine on days 1 and 8, oral capecitabine twice daily on days 1-14, and oral sunitinib daily for six 21-day cycles, followed by sunitinib monotherapy at the investigator's discretion. Dose level 0 (DL0) was gemcitabine 1,000 mg/m(2) per day plus capecitabine 650 mg/m(2) per 12 hours plus sunitinib 37.5 mg/day; DL1 was gemcitabine 1,000 mg/m(2) per day plus capecitabine 850 mg/m(2) per 12 hours plus sunitinib 37.5 mg/day. RESULTS: Sixteen patients were enrolled. At DL1, two of four patients had dose-limiting toxicity (DLT; grade 3 diarrhea and grade 4 thrombocytopenia). The dose was reduced to DL0 when only 1 of 12 patients experienced DLT (grade 3 diarrhea, grade 3 mucositis, and grade 3 thrombocytopenia). Dose reductions were frequent (58% of patients), and only seven patients were able to receive the three drugs for more than three cycles. One patient achieved a complete response, three had partial responses, and the best response for four was stable disease. CONCLUSION: The safety profile of the combination does not seem manageable in this patient population. No further development of the combination is recommended.

Sequential targeted therapy after pazopanib therapy in patients with metastatic renal cell cancer: efficacy and toxicity.

INTRODUCTION/BACKGROUND: Patients with metastatic renal cell carcinoma (mRCC) in whom first-line therapies have failed might derive clinical benefit with sequential targeted agents. Limited data are available on the efficacy and toxicity of subsequent therapies after disease progression during pazopanib therapy. PATIENTS AND METHODS: Patients with mRCC who received subsequent systemic treatment after pazopanib treatment failure were identified across 7 institutions. Pazopanib was given as first-line therapy in 28 patients and after cytokines therapy in 7 patients. Clinical outcome and toxicity analyses of 2 sequential treatment options (anti-vascular endothelial growth factor [VEGF] or mammalian target of rapamycin inhibitor [mTORi]) is presented. RESULTS: Subsequent therapy was anti-VEGF in 22 patients and mTORi in 13. One patient who received bevacizumab and temsirolimus combination was excluded. VEGF-targeted therapies included sorafenib (n = 10), sunitinib (n = 3), bevacizumab (n = 2), cediranib (n = 4) and cabozantinib (n = 3). Patients treated with mTORi received everolimus. Median progression-free survival was 5.6 months from the start of subsequent therapy with anti-VEGF and 2.4 months with mTORi (P = .009). Overall survival (OS) was not significantly different (P = .68). Clinical benefit (including partial response and stable disease) on subsequent therapy was observed in 15 patients (64%) and 4 patients (31%) of anti-VEGF- and everolimus-treated patients, respectively (P = .021). CONCLUSION: In this retrospective study, targeting VEGF was an effective strategy after disease progression during pazopanib treatment, although OS was not different among patients treated with VEGF or mTORi.

Sunitinib malate in the treatment of urothelial cancer.

INTRODUCTION: Urothelial cancer (UC) is the fourth most common cancer in men, worldwide. After cystectomy, muscle invasive disease progresses up to 50%, either regionally or as distant metastases, and treatment of metastatic disease remains a challenge, with a median survival that not exceeded 14 months with current chemotherapy regimens. Angiogenesis has been shown to play a role in UC progression and targeting this pathway may improve treatment outcomes. Sunitinib , an anti-angiogenic tyrosine kinase inhibitor, has been tested in preclincal models and Phase II trials in UC. AREAS COVERED: In this review, the authors discuss the rational for targeting angiogenesis pathway in UC with sunitinib. They also discuss its mechanisms of action, and the data from its preclinical and clinical data studies. EXPERT OPINION: Sunitinib monotherapy has clinical activity in UC, identifying the potential role of the angiogenic pathway as a target for therapy in this tumor type. However, overlapping toxicity with chemotherapy has limited further development. Future research should be focused on improving patient selection which is based on the identification of validated predictive markers for sunitinib treated patients.

Level of HER2 gene amplification predicts response and overall survival in HER2-positive advanced gastric cancer treated with trastuzumab.

PURPOSE: Previous studies have highlighted the importance of an appropriate human epidermal growth factor receptor 2 (HER2) evaluation for the proper identification of patients eligible for treatment with anti-HER2 targeted therapies. Today, the relationship remains unclear between the level of HER2 amplification and the outcome of HER2-positive gastric cancer treated with first-line chemotherapy with trastuzumab. The aim of this study was to determine whether the level of HER2 gene amplification determined by the HER2/CEP17 ratio and HER2 gene copy number could significantly predict some benefit in overall survival and response to therapy in advanced gastric cancer treated with trastuzumab-based chemotherapy. PATIENTS AND METHODS: Ninety patients with metastatic gastric cancer treated with first-line trastuzumab-based chemotherapy were studied. The optimal cutoff values for HER2/CEP17 ratio and HER2 gene copy number (GCN) for discriminating positive results in terms of response and prolonged survival were determined using receiver operating characteristic curves analyses. RESULTS: In this study, a median HER2/CEP17 ratio of 6.11 (95% CI, 2.27 to 21.90) and a median HER2 gene copy number of 11.90 (95% CI, 3.30 to 43.80) were found. A mean HER2/CEP17 ratio of 4.7 was identified as the optimal cutoff value discriminating sensitive and refractory patients (P = .005). Similarly, the optimal cutoff for predicting survival longer than 12 months was 4.45 (P = .005), and for survival longer than 16 months was 5.15 (P = .004). For HER2 GCN, the optimal cutoff values were 9.4, 10.0, and 9.5, respectively (P = .02). CONCLUSION: The level of HER2 gene amplification significantly predicts sensitivity to therapy and overall survival in advanced gastric cancer treated with trastuzumab-based chemotherapy.

Molecular determinants of response to cisplatin-based neoadjuvant chemotherapy.

PURPOSE OF REVIEW: Neoadjuvant chemotherapy followed by cystectomy improves survival compared with surgery alone. To prevent overtreatment is of outmost importance to define molecular predictors of response for patient selection. We present the currently available data outlining a variety of potential markers to aid for a personalized decision-making process. RECENT FINDINGS: Apart from p53, other markers of cell cycle regulation and apoptosis such as p21WAF1/CIP1 (p21) gene, Bcl-2, mouse double minute-2 and pRB have also been related to survival. The clinical relevance of epidermal growth factor receptor and HER2 expression has also been investigated with no success. Regarding Ki67, overexpressing tumors may potentially benefit from neoadjuvant therapy and conversely overexpression of vascular endothelial growth factor and bFGF have been linked to resistance to cisplatin-induced apoptosis. The role of multidrug resistance gene 1 and excision repair cross-complementing rodent repair deficiency complementation group 1 supports that enhanced DNA repair in the tumor decreases the benefit of platinum-based treatment. A 20-gene expression model has shown to predict lymph node involvement, helping on decision-making. A gene expression profiling has been proposed as predictive for response to neoadjuvant chemotherapy. SUMMARY: Predictive markers will eventually aid in the selection of patients that most likely benefit from preoperative treatment. In the coming years, a panel of markers will become available to achieve the predicted goal.

Incomplete staging surgery as a major predictor of relapse of borderline ovarian tumor.

BACKGROUND: Borderline ovarian tumors (BOTs) are a subset of epithelial ovarian tumors with low malignant potential but significant risk of relapse (10% to 30%). Unfortunately, surgical prognostic factors for BOT relapse have not been clearly identified, probably due to the use of heterogeneous surgical definitions and limited follow-up. The aim of this study was to assess potential relapse risk factors using standard surgical definitions and long follow-up. METHODS: All patients diagnosed with BOT for a period of more than 10 years in a single institution were included in the analysis. Complete surgical staging was defined as the set of procedures that follow standard guidelines for staging surgery (except lymphadenectomy), performed either with one or two interventions. Fertility-sparing surgeries that preserved one ovary and the uterus but included all the remaining procedures were classified as complete staging. The relationship between potential risk factors and time to BOT relapse was assessed by log-rank tests corrected for multiple comparisons and Cox regression. RESULTS: Forty-six patients with a median follow-up of 5.4 years were included, of whom 91.3% had been diagnosed as FIGO stage I disease and 45.7% had received complete staging surgery. Five relapses were detected (10.9%), all of them in women who had been diagnosed with stage I disease and had received incomplete staging surgery. Log-rank tests confirmed the association between incomplete staging surgery and shorter time to BOT relapse. CONCLUSIONS: Complete staging surgery should be considered a cornerstone of BOT treatment in order to minimize the risk of relapse.

Salud, hostelería e industria del tabaco / Health, hospitality sector and tobacco industry

Poner de manifiesto las estrategias empleadas por la industria tabaquera para hacer frente a las medidas gubernamentales de regulación de sus productos. Evidenciar la relación existente entre la industria del tabaco y el sector de la hostelería. Constatar que los argumentos y estrategias utilizados de manera habitual por la industria hostelera han sido previamente aportados por la industria del tabaco. Localización de documentos claves mediante metabuscadores, enlaces a sitios de documentos desclasificados, documentos de webs específicas sobre tabaco y del sector de la hostelería, fuentes periodísticas y artículos científicos publicados en revistas especializadas en salud. Se pone en evidencia la estrecha relación entre industria del tabaco y el sector hostelero. Se ponen de manifiesto las estrategias llevadas a cabo por la industria del tabaco que incluyen acaparación de información estratégica, relaciones públicas, lobbys, programa de consultoría, grupos de defensa de los fumadores, creación de alianzas, intimidación y patrocinio. Los argumentos y estrategias utilizados por la industria de la hostelería coinciden punto por punto con los utilizados por la industria del tabaco. Estos argumentos son rebatibles desde el punto de vista de la Salud Pública, ya que científicamente está totalmente comprobado que los ambientes libres de humo son la única manera de proteger a los no fumadores de la exposición al humo del tabaco y de sus efectos nocivos sobre la salud(AU)

To present the strategies used by the tobacco industry to meet government regulatory measures of its products. To demonstrate the relationship between tobacco industry and the hospitality sector. Note that the arguments and strategies used routinely by the hospitality industry have been previously provided by the tobacco industry. Location of key documents by meta-search, links to declassified documents, specific websites of the tobacco and hospitality industry, news sources and published articles in health journals. This review reveals the close relationship between tobacco industry and hospitality sector. It highlights the strategies carried out by the tobacco industry, including strategic hoarding of information, public relations, lobbying, consultation program, smoker defence groups, building partnerships, intimidation and patronage. The arguments and strategies used by the hospitality industry to match point by point that used by the tobacco industry. These arguments are refutable from the point of view of public health as it is scientifically proven that totally smoke-free environments are the only way to protect non-smokers from tobacco smoke exposure and its harmful effects on health(AU)

[Health, hospitality sector and tobacco industry]. / Salud, hostelería e industria del tabaco.

To present the strategies used by the tobacco industry to meet government regulatory measures of its products. To demonstrate the relationship between tobacco industry and the hospitality sector. Note that the arguments and strategies used routinely by the hospitality industry have been previously provided by the tobacco industry. Location of key documents by meta-search, links to declassified documents, specific websites of the tobacco and hospitality industry, news sources and published articles in health journals. This review reveals the close relationship between tobacco industry and hospitality sector. It highlights the strategies carried out by the tobacco industry, including strategic hoarding of information, public relations, lobbying, consultation program, smoker defence groups, building partnerships, intimidation and patronage. The arguments and strategies used by the hospitality industry to match point by point that used by the tobacco industry. These arguments are refutable from the point of view of public health as it is scientifically proven that totally smoke-free environments are the only way to protect non-smokers from tobacco smoke exposure and its harmful effects on health.

Optimisation of the size variation threshold for imaging evaluation of response in patients with platinum-refractory advanced transitional cell carcinoma of the urothelium treated with vinflunine.

BACKGROUND: Vinflunine (VFL) has been approved in the European Union for second-line treatment of advanced transitional cell carcinoma of the urothelial tract (TCCU) in patients who progress after a platinum based regimen. However, very few patients achieve response by response evaluation criteria in solid tumours (RECIST). Therefore, another 'response' threshold may be more useful than RECIST 1.0 in this setting. METHODS: One hundred and seventy nine patients with advanced TCCU treated with second-line VFL therapy had chest Computed Tomography (CT) and abdominal/pelvic CT or MRI performed at baseline and at first follow-up (6 weeks ± 3 days) after therapy initiation. Tumour measurements and response by RECIST 1.0 were correlated with overall survival (OS). Kaplan-Meier and receiver operating characteristic (ROC) analysis were then used to determine the optimal size threshold to define 'responders'. Impact of adverse prognostic factors including Eastern Cooperative Oncology Group Performance Status (ECOG PS) >0, Hb <10 g/dL, and liver metastases was analysed. RESULTS: Tumour response included 13 partial responses (PR) by RECIST 1.0 and 52 patients with ≥ 10% decrease in the sum of longest diameters. Responders by RECIST 1.0 did not have a statistically significant improvement in OS, while patients with sum long axis diameter (SLD) reduction of ≥ 10% had a longer OS than those with SLD reduction of <10%: 11.3 versus 6.9 months (log rank p=0.0224). ROC analysis yielded ≥ 10% decrease in SLD as the optimal size change correlating with OS. These results persisted on multivariate analysis. CONCLUSION: In the study population, a ≥ 10% reduction in SLD at first follow-up imaging is a better early predictor of outcome than RECIST.

Metastatic uveal melanoma: is there a role for conventional chemotherapy? - A single center study based on 58 patients.

Uveal melanoma metastases develop in 6.5-35% of patients, most commonly to the liver. Metastatic uveal melanoma (MUM) survival is poor, with 5-7 months of median survival. We reviewed retrospectively all patients with MUM diagnosed between January 1990 and December 2008 at our institution. We analyzed a total of 58 patients with a median age of 61 years (31-84 years). Median time for metastases development was 25.63 months (0.17-102.43 months). Fifty-six patients had hepatic involvement, 63.8% bilobar and 51.7% had more than or equal to five hepatic metastatic lesions. Sixteen patients (27.6%) had two or more organs involved. Six patients (10.71%) were treated with surgery, 25 patients (44.67%) received systemic chemotherapy, and 23 (41.07%) had best supportive care (BSC). The median overall survival (OS) for all the patients was 10.83 months [95% confidence interval (CI): 6.92-14.74]. Patients who had undergone chemotherapy presented 10.83 months (95% CI: 5.35-16.308) of median OS whereas the patients who did not undergo this treatment had an OS of 8.033 months (95% CI: 2.46-13.61). There were more patients with poor survival characteristics such as worse Eastern Cooperative Oncology Group performance status in the BSC group. OS was poor in treated and BSC patients. Differences in survival are more likely to be related to patient characteristics rather than to a chemotherapy effect. Patients with MUM should be included in clinical trials evaluating other options with newer agents.

Variant forms of bladder cancer: basic considerations on treatment approaches.

Variant forms of bladder cancer are non-urothelial neoplasms or urothelial carcinomas mixed with other histologies. Compared to pure urothelial carcinoma, they all present with a high stage and grade. Prognosis is variable and there is a lack of evidence regarding the ideal treatment approach, because of their relative infrequency and the noninclusion in bladder cancer randomized trials. Despite this, basic recommendations can be extracted from case series. In the present report, existent literature about variant forms of bladder cancer is reviewed with focus on the most frequent: squamous cell, adenocarcinoma, small cell, micropapillary, sarcomatoid, and lymphoepithelioma-like.

Trauma infantil y esquizofrenia / Childhood trauma and schizophrenia

Introducción: La prevalencia de antecedentes de trauma en la psicobiografía de los pacientes psicóticos es alta, hasta el punto de que algunos autores defienden que hay un subgrupo de esquizofrenia, la esquizofrenia traumática inducida, que se caracterizaría por la preponderancia de los síntomas psicóticos positivos. Observación clínica: Presentamos el caso de una paciente joven que sufrió abusos sexuales repetidos en su infancia y que desarrolló, a los 19 años, una esquizofrenia. El inicio de la enfermedad fue con alucinaciones auditivas sobre el abusador, sintomatología depresiva e ideación delirante de autorreferencia y de control del pensamiento que obligó a un ingreso hospitalario. Durante los 7 años de curso de la enfermedad, siempre presentó alucinaciones auditivas, cenestésicas y visuales, en ocasiones relacionadas con los abusos y en otras, no. Destaca también la ausencia de síntomas negativos. Discusión: La alta prevalencia de trauma infantil en pacientes psicóticos hace pensar en que el abuso grave podría ser uno de los factores ambientales que influyen en el desarrollo de la esquizofrenia. Una delas consecuencias de este hecho es la necesidad de indagar de forma sistemática en las posibles experiencias traumáticas en la biografía de cualquier paciente que se nos presente con sintomatología psicótica (AU)

Introduction: The prevalence of a history of trauma in the psychobiography of psychotic patients is high, and some authors argue for the existence of a subtype of schizophrenia, trauma-induced schizophrenia, characterized by a preponderance ofpositive psychotic symptoms.Case report: We report the case of a Young female patient who suffered repeated sexual abuse in childhood and developed schizophrenia at the age of nineteen. The presenting symptoms of the disease consisted of auditory hallucinations that spoke of her abuser, depressive symptoms and delusional ideationand thought control, leading to hospitalization. During the 7-year course of the disease, the patient has always experienced auditory, visual and kinesthetic hallucinations, sometimes -but not always- related to abuse. A striking feature is the absence of negative symptoms. Discussion: The high prevalence of childhood trauma in psychotic patients suggests that serious abuse could be one of the environmental factors influencing the development of schizophrenia. One consequence of this finding is the need to routinely investigate any traumatic experiences in the life of any patient with psychotic symptoms (AU)