Tailoring treatment for elderly bladder cancer: a case report of personalized management of high-grade urothelial carcinoma with papillary features.

This case study presents the diagnostic and therapeutic course of a 72-year-old male patient with a history of high-grade urothelial carcinoma with papillary features. The report outlines the patient's initial presentation, the intervention strategies employed, including transurethral resection and intravesical Bacillus Calmette-Guérin (BCG) therapy, the subsequent complications and clinical decisions following the intense symptoms post-treatment. The study highlights the challenges in managing bladder cancer in elderly patients, considering the tumor's characteristics, treatment responses, and the patient's quality of life.

Characteristics and Survival Outcomes of Patients With Metastatic RET Fusion-Positive Solid Tumors Receiving Non-RET Inhibitor Standards of Care in a Real-World Setting.

PURPOSE: RET fusions are oncogenic drivers across different solid tumors. However, the genomic landscape and natural history of patients with RET fusion-positive solid tumors are not well known. We describe the clinical characteristics of RET tyrosine kinase inhibitor (TKI)-naïve patients with RET fusion-positive solid tumors (excluding non-small-cell lung cancer [NSCLC]), treated in a real-world setting and assess the prognostic effect of RET fusions. METHODS: Data for RET TKI-naïve patients with metastatic solid tumors (excluding NSCLC) who had ≥one Foundation Medicine comprehensive genomic profiling test (January 1, 2011-March 31, 2022) were obtained from a deidentified nationwide (US-based) clinicogenomic database. The primary objective of this study was to compare the overall survival (OS) of patients with RET fusion-positive tumors versus matched patients with RET wild-type (RET-WT) tumors. Patients with RET-WT solid tumors were matched (4:1) to patients with RET fusion-positive tumors on the basis of preselected covariates. RESULTS: The study population included 26 patients in the RET fusion-positive cohort, 7,220 patients in the RET-WT cohort (before matching), and 104 patients in the matched RET-WT cohort. Co-occurring genomic alterations were rare in the RET fusion-positive cohort. Median OS was consistently lower in patients with RET fusion-positive tumors versus those with RET-WT tumors, using three different analyses (hazard ratios, 2.0, 1.7, and 2.2). CONCLUSION: These data suggest that RET fusions represent a negative prognostic factor in patients with metastatic solid tumors and highlight the need for wider genomic testing and use of RET-specific TKIs that could improve patient outcomes. Our study also highlights the value of real-world data when studying rare cancers or cancers with rare genomic alterations.

Current trends in cancer immunotherapy: a literature-mining analysis.

Cancer immunotherapy is a rapidly growing field that is completely transforming oncology care. Mining this knowledge base for biomedically important information is becoming increasingly challenging, due to the expanding number of scientific publications, and the dynamic evolution of this subject with time. In this study, we have employed a literature-mining approach that was used to analyze the cancer immunotherapy-related publications listed in PubMed and quantify emerging trends. A total of 93,033 publications published in 5055 journals have been retrieved, and 141 meaningful topics have been identified, which were further classified into eight distinct categories. Statistical analysis indicates a mean annual increase in the number of published papers of approximately 8% in the last 20 years. The research topics that exhibited the highest trends included "immune checkpoint inhibitors," "tumor microenvironment," "HPV vaccination," "CAR T-cells," and "gene mutations/tumor profiling." The top identified cancer types included "lung," "colorectal," and "breast cancer," and a shift in popularity from hematological to solid tumors was observed. As regards clinical research, a transition from early phase clinical trials to randomized control trials was recorded, indicating that the field is entering a more advanced phase of development. Overall, this mining approach provided an unbiased analysis of the cancer immunotherapy literature in a time-conserving and scale-efficient manner.

Disparities in genetic services utilization in a random sample of young breast cancer survivors.

PURPOSE: Increasing use of genetic services (counseling/testing) among young breast cancer survivors (YBCS) can help decrease breast cancer incidence and mortality. The study examined use of genetic services between Black and White/Other YBCS, attitudes and knowledge of breast cancer risk factors, and reasons for disparities in using genetic services. METHODS: We used baseline data from a randomized control trial including a population-based, stratified random sample of 3000 potentially eligible YBCS, with oversampling of Black YBCS. RESULTS: Among 883 YBCS (353 Black, 530 White/Other) were significant disparities between the two racial groups. More White/Other YBCS had received genetic counseling and had genetic testing than Blacks. Although White/Other YBCS resided farther away from board-certified genetic counseling centers, they had fewer barriers to access these services. Black race, high out-of-pocket costs, older age, and more years since diagnosis were negatively associated with use of genetic services. Black YBCS had lower knowledge of breast cancer risk factors. Higher education and genetic counseling were associated with higher genetic knowledge. CONCLUSION: Racial inequalities of cost-related access to care and education create disparities in genetic services utilization. System-based interventions that reduce socioeconomic disparities and empower YBCS with genetic knowledge, as well as physician referrals, can increase access to genetic services.

Predictors and interdependence of family support in a random sample of long-term young breast cancer survivors and their biological relatives.

OBJECTIVE: Women diagnosed with breast cancer younger than 45 years (young breast cancer survivors-YBCS) and their biological relatives face significant stressors. Although family support is an important coping resource, little is known about YBCS' and relatives' support and whether it is interdependent. The study described family support in YBCS and their biological relatives; identified demographic, clinical, and psychosocial predictors of support; and determined the interdependence of support in YBCS-relatives family units. METHODS: Data were collected from a random sample of YBCS and their first- or second-degree female relatives. Actor-partner interdependence models (APIM) explored predictors and interdependence of YBCS' and relatives' family support in dyads (YBCS and relative) and triads (YBCS and two relatives). RESULTS: Among n = 310 YBCS and n = 431 first- or second-degree relatives, family support was higher in triads compared to dyads. APIMs identified actor effects in dyads, and actor and partner effects in triads. Across all family units, YBCS' higher self-efficacy was associated with higher YBCS support (actor effect) and relative support (partner effect); YBCS' prior diagnosis of depression was associated with lower YBCS and relative support (actor and partner effect); cost-related lack of access to care was associated with lower support among YBCS (actor effect) and relatives (actor and partner effect). CONCLUSIONS: Family support was interdependent and was affected by self-efficacy, depression, and access to care. Interventions should include YBCS and relatives, enhance self-efficacy and access to care.

Challenges and Opportunities for Cancer Predisposition Cascade Screening for Hereditary Breast and Ovarian Cancer and Lynch Syndrome in Switzerland: Findings from an International Workshop.

BACKGROUND: An international workshop on cancer predisposition cascade genetic screening for hereditary breast and ovarian cancer (HBOC) and Lynch syndrome (LS) took place in Switzerland, with leading researchers and clinicians in cascade screening and hereditary cancer from different disciplines. The purpose of the workshop was to enhance the implementation of cascade genetic screening in Switzerland. Participants discussed the challenges and opportunities associated with cascade screening for HBOC and LS in Switzerland (CASCADE study); family implications and the need for family-based interventions; the need to evaluate the cost-effectiveness of cascade genetic screening; and interprofessional collaboration needed to lead this initiative. METHODS: The workshop aims were achieved through exchange of data and experiences from successful cascade screening programs in the Netherlands, Australia, and the state of Ohio, USA; Swiss-based studies and scientific experience that support cancer cascade screening in Switzerland; programs of research in psychosocial oncology and family-based studies; data from previous cost-effectiveness analyses of cascade genetic screening in the Netherlands and in Australia; and organizational experience from a large interprofessional collaborative. Scientific presentations were recorded and discussions were synthesized to present the workshop findings. RESULTS: The key elements of successful implementation of cascade genetic screening are a supportive network of stakeholders and connection to complementary initiatives; sample size and recruitment of relatives; centralized organization of services; data-based cost-effectiveness analyses; transparent organization of the initiative; and continuous funding. CONCLUSIONS: This paper describes the processes and key findings of an international workshop on cancer predisposition cascade screening, which will guide the CASCADE study in Switzerland.

Cancer Predisposition Cascade Screening for Hereditary Breast/Ovarian Cancer and Lynch Syndromes in Switzerland: Study Protocol.

BACKGROUND: Breast, colorectal, ovarian, and endometrial cancers constitute approximately 30% of newly diagnosed cancer cases in Switzerland, affecting more than 12,000 individuals annually. Hundreds of these patients are likely to carry germline pathogenic variants associated with hereditary breast ovarian cancer (HBOC) or Lynch syndrome (LS). Genetic services (counseling and testing) for hereditary susceptibility to cancer can prevent many cancer diagnoses and deaths through early identification and risk management. OBJECTIVE: Cascade screening is the systematic identification and testing of relatives of a known mutation carrier. It determines whether asymptomatic relatives also carry the known variant, needing management options to reduce future harmful outcomes. Specific aims of the CASCADE study are to (1) survey index cases with HBOC or LS from clinic-based genetic testing records and determine their current cancer status and surveillance practices, needs for coordination of medical care, psychosocial needs, patient-provider and patient-family communication, quality of life, and willingness to serve as advocates for cancer genetic services to blood relatives, (2) survey first- and second-degree relatives and first-cousins identified from pedigrees or family history records of HBOC and LS index cases and determine their current cancer and mutation status, cancer surveillance practices, needs for coordination of medical care, barriers and facilitators to using cancer genetic services, psychosocial needs, patient-provider and patient-family communication, quality of life, and willingness to participate in a study designed to increase use of cancer genetic services, and (3) explore the influence of patient-provider communication about genetic cancer risk on patient-family communication and the acceptability of a family-based communication, coping, and decision support intervention with focus group(s) of mutation carriers and relatives. METHODS: CASCADE is a longitudinal study using surveys (online or paper/pencil) and focus groups, designed to elicit factors that enhance cascade genetic testing for HBOC and LS in Switzerland. Repeated observations are the optimal way for assessing these outcomes. Focus groups will examine barriers in patient-provider and patient-family communication, and the acceptability of a family-based communication, coping, and decision-support intervention. The survey will be developed in English, translated into three languages (German, French, and Italian), and back-translated into English, except for scales with validated versions in these languages. RESULTS: Descriptive analyses will include calculating means, standard deviations, frequencies, and percentages of variables and participant descriptors. Bivariate analyses (Pearson correlations, chi-square test for differences in proportions, and t test for differences in means) will assess associations between demographics and clinical characteristics. Regression analyses will incorporate generalized estimating equations for pairing index cases with their relatives and explore whether predictors are in direct, mediating, or moderating relationship to an outcome. Focus group data will be transcribed verbatim and analyzed for common themes. CONCLUSIONS: Robust evidence from basic science and descriptive population-based studies in Switzerland support the necessity of cascade screening for genetic predisposition to HBOC and LS. CASCADE is designed to address translation of this knowledge into public health interventions. TRIAL REGISTRATION: ClinicalTrials.gov NCT03124212; https://clinicaltrials.gov/ct2/show/NCT03124212 (Archived by WebCite at http://www.webcitation.org/6tKZnNDBt).

Pharmacotherapy in smoking cessation: Corticotropin Releasing Factor receptors as emerging intervention targets.

Smoking represents perhaps the single most important health risk factor and a global contributor to mortality that can unquestionably be prevented. Smoking is responsible for many diseases, including various types of cancer, chronic obstructive pulmonary disease, coronary heart disease, peripheral vascular disease and peptic ulcer, while it adversely affects fetal formation and development. Since smoking habit duration is a critical factor for mortality, the goal of treatment should be its timely cessation and relapse prevention. Drug intervention therapy is an important ally in smoking cessation. Significant positive steps have been achieved in the last few years in the development of supportive compounds. In the present review, we analyze reports studying the role of Corticotropin Releasing Factor (CRF), the principle neuroendocrine mediator of the stress response and its two receptors (CRF1 and CRF2) in the withdrawal phase as well as in the abstinence from nicotine use. Although still in pre-clinical evaluation, therapeutic implications of these data were investigated in order to highlight potential pharmaceutical interventions.

Recruiting families at risk for hereditary breast and ovarian cancer from a statewide cancer registry: a methodological study.

PURPOSE: Cancer genetic services (counseling/testing) are recommended for women diagnosed with breast cancer younger than 45 years old (young breast cancer survivors-YBCS) and at-risk relatives. We present recruitment of YBCS, identification and recruitment of at-risk relatives, and YBCS willingness to contact their cancer-free, female relatives. METHODS: A random sample of 3,000 YBCS, stratified by race (Black vs. White/Other), was identified through a population-based cancer registry and recruited in a randomized trial designed to increase use of cancer genetic services. Baseline demographic, clinical, and family characteristics, and variables associated with the Theory of Planned Behavior (TPB) were assessed as predictors of YBCS' willingness to contact at-risk relatives. RESULTS: The 883 YBCS (33.2% response rate; 40% Black) who returned a survey had 1,875 at-risk relatives and were willing to contact 1,360 (72.5%). From 853 invited at-risk relatives (up to two relatives per YBCS), 442 responded (51.6% response rate). YBCS with larger families, with a previous diagnosis of depression, and motivated to comply with recommendations from family members were likely to contact a greater number of relatives. Black YBCS were more likely to contact younger relatives and those living further than 50 miles compared to White/Other YBCS. CONCLUSION: It is feasible to recruit diverse families at risk for hereditary cancer from a population-based cancer registry. This recruitment approach can be used as a paradigm for harmonizing processes and increasing internal and external validity of large-scale public health genomic initiatives in the era of precision medicine.

Regional disparities in cancer mortality across the rural-urban axis: a case study from north-eastern Greece.

INTRODUCTION: The aim of this study was to identify differences in cancer mortality in north-eastern Greece, to describe potential drivers operating at the population level and to propose practical interventions and mitigation strategies. METHODS: Cancer mortality data were collected from local registries using the WHO 10th edition of International Classification of Disease (ICD-10). The direct standardization method was used to address demographic differences in the two regions, with the Standard European Population as reference. Rate ratios (RR) were employed for comparisons and 95% confidence intervals (95%CI) were calculated according to the Poisson approximation method. RESULTS: An increased risk of digestive system cancers (excluding liver neoplasms) was observed in rural versus urban areas (RR=1.25, 95%CI=1.02-1.54). Stomach cancer, in particular, was more prevalent in the older cohorts (>65 years), suggesting a historical epidemiological perspective. A more pronounced discrepancy was observed for prostate cancer mortality (RR=1.86, 95%CI=1.10-3.14), indicating a strong positive correlation with rurality. CONCLUSIONS: Cancer mortality disparities have been observed between rural and urban regions of north-eastern Greece. Health promotion and education, including improved access to medical facilities and early cancer screening, can help mitigate the burden and extend survival rates. Decreasing cancer staging at the time of diagnosis and reversing social and economic inequalities is key for combating these types of malignancy.

PAX1 methylation as an auxiliary biomarker for cervical cancer screening: a meta-analysis.

OBJECTIVE: Several studies have implicated PAX1 epigenetic regulation in cervical neoplasia. The aim of this meta-analysis was to assess PAX1 gene methylation as a potential biomarker in cervical cancer screening. METHODS: A systematical search of all major databases was performed, in order to include all relevant publications in English until December 31(st) 2014. Studies with insufficient data, conducted in experimental models or associated with other comorbidities were excluded from the meta-analysis. Summary receiver operating characteristics (SROC) for Cervical Intraepithelial Neoplasia grade 2 or worse (CIN2(+)) versus normal, and CIN grade 3 or worse (CIN3(+)) versus normal, were estimated using the bivariate model. RESULTS: Out of the 20 initially included studies, finally 7 (comprising of 1385 subjects with various stages of CIN and normal cervical pathology) met the inclusion criteria. The sensitivity of CIN2(+) versus normal was estimated to be 0.66 (CI 95%, 0.46-0.81) and the specificity 0.92 (CI 95%, 0.88-0.95). On the other hand, the sensitivity of CIN3(+) versus normal was 0.77 (CI 95%, 0.58-0.89) and the specificity 0.92 (CI 95%, 0.88-0.94). Moreover, the area under the curve (AUC) in the former case was 0.923, and in the latter 0.931. CONCLUSION: The results of this meta-analysis support the utility of PAX1 methylation as an auxiliary biomarker in cervical cancer screening. PAX1 could be used effectively to increase the specificity of HPV DNA by detecting women with more advanced cervical abnormalities.

Caries prevalence and manganese and iron levels of drinking water in school children living in a rural/semi-urban region of North-Eastern Greece.

OBJECTIVE: The aim of this study was to correlate different combinations of manganese (Mn) and iron (Fe) concentration in drinking water with prevalence of dental caries in both primary and permanent dentition, among school children with similar socio-demographic characteristics. METHODS: Evros region, in North-Eastern Greece, was divided into four areas, according to combinations of levels of Mn and Fe in drinking water (High Mn-high Fe; High Mn-low Fe; Low Mn-high Fe; Low Mn-low Fe). Children of similar socio-economic background, attending either first or sixth grade (primary or permanent dentition, respectively) of elementary schools, were clinically assessed for caries by three dentists. Caries was defined by the use of dmft/DMFT index. A questionnaire answered by the parents was also analysed. RESULTS: 573 children were included. Caries prevalence was high in both age groups (64.2 % with mean dmft 3.3 ± 3.6 in primary and 60.7 % with mean DMFT 2.3 ± 2.5 in permanent dentition, respectively). Residence in a high Mn-low Fe area was associated with a significant OR for caries in both age groups [OR (95 % CIs) for primary and permanent dentition was, respectively, 3.75 (1.68-8.37), p = 0.001 and 3.09 (1.48-6.44), p = 0.003], independently of factors like sugar consumption or brushing frequency. CONCLUSION: Prevalence of caries was high in general, and was associated with the combination of high Mn/low Fe levels in drinking water, independently of various socio-demographic factors.

Public health risk assessment associated with heavy metal and arsenic exposure near an abandoned mine (Kirki, Greece).

The 'Agios Philippos' lead-zinc mine in the Kirki region (NE Greece) is now closed, but its legacy of heavy metal contamination remains at the site. At present, management of the contaminated land is of major concern. The area is in a reclamation process and requires immediate remediation action, whereas human risks need to be carefully evaluated. In order to assess these risks, samples from around the mine were collected and analyzed and a scenario involving the oral, dermal, and inhaled doses of arsenic and heavy metals was formulated. A Monte Carlo approach was undertaken, in order to model the average daily dose and quantify the corresponding hazard index and cancer risk. A toxicological risk was associated with samples collected in the vicinity of the mine (floatation, mine tailings) and a pronounced carcinogenic risk for arsenic was evident at the broader occupational/environmental setting. These findings urge for immediate rehabilitation actions that will mitigate population exposures and promote long-term environmental safety in the area.

Diferenças na mortalidade por câncer rural/urbana: um estudo de caso do nordeste da Grécia / Rural/urban disparities in cancer mortality: a case-study from northeast Greece

Uma abordagem epidemiológica descritiva foi realizada a fim de abordar a questão das disparidades rural/urbana da mortalidade por câncer no nordeste da Grécia. O método de normalização direta foi usado para controlar as diferenças na distribuição da faixa etária entre as duas regiões. A região A era altamente urbanizada (>90%) e a região B, predominantemente, agrícola. O registro dos casos foi realizado de acordo com o protocolo da CID10 da Organização Mundial de Saúde. Foram observados resultados estatisticamente significativos para mortalidade por câncer de próstata, que foi 86% maior na área rural em oposição aos indivíduos de áreas urbanas (RR=1,86, IC95% 1,10?3,14). Em outros tipos de câncer (por exemplo, câncer de estômago) um efeito coorte pode estar presente, necessitando assim mais investigações sobre a hipótese. Desigualdades socioeconômicas, tais como acesso a cuidados de saúde e educação, são fatores fundamentais para a erradicação das disparidades rural/urbana na mortalidade por câncer. As intervenções devem centrar-se na promoção da saúde e conscientização, especialmente abordando a importância do rastreamento precoce e diagnóstico de câncer.

Denitrifying polyphosphate accumulating organisms population and nitrite reductase gene diversity shift in a DEPHANOX-type activated sludge system fed with municipal wastewater.

Enhanced biological phosphorus removal (EBPR) is a widely applied method for nutrients removal, although little is known about the key genes regulating the complex biochemical transformations occurring in activated sludge during phosphorus removal. In the present study, the nitrite reductase gene (nirS) diversity and the denitrifying polyphosphate accumulating organisms (DPAOs) population, grown in a bench scale, two-sludge, continuous flow plant, operating for biological anoxic phosphorus removal (DEPHANOX-type), fed with municipal wastewater, were examined by means of physicochemical analyses and the application of molecular techniques. The DEPHANOX configuration highly influenced biomass phosphorus as well as polyhydroxyalkanoates content and facilitated the enrichment of the DPAOs population. The application of double probe fluorescent in situ hybridization (double probe FISH) technique revealed that DPAOs comprised 20% of the total bacterial population. Based on clone libraries construction and nirS gene sequencing analysis, a pronounced shift in denitrifying bacteria diversity was identified during activated sludge acclimatization. Moreover, nirS gene sequences distinct from those detected in any known bacterial strain or environmental clone were identified. This is the first report studying the microbial properties of activated sludge in a DEPHANOX-type system using molecular techniques.