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Integrins are heterodimeric cell surface receptors that bind to different extracellular ligands depending on their composition and regulate all processes which enable multicellular life. In cancer, integrins trigger and play key roles in all the features that were once described as the Hallmarks of Cancer. In this review, we will discuss the contribution of integrins to these hallmarks, including uncontrolled and limitless proliferation, invasion of tumor cells, promotion of tumor angiogenesis and evasion of apoptosis and resistance to growth suppressors, by highlighting the latest findings. Further on, given the paramount role of integrins in cancer, we will present novel strategies for integrin inhibition that are starting to emerge, promising a hopeful future regarding cancer treatment.

Background: Nanoliposomal irinotecan (nal-IRI) plus 5-fluorouracil/leucovorin (5-FU/LV) is a novel treatment option for gemcitabine-pretreated metastatic pancreatic adenocarcinoma (PAC) patients, but real-world evidence is rare. Our aim was to determine the effectiveness and tolerability of this regimen in advanced PAC patients and to compare it with oxaliplatin plus fluoropyrimidines in the second-line setting after failure of gemcitabine. Methods: This is a retrospective single-center analysis of all patients who have been treated with nal-IRI plus 5-FU/LV. To compare its effectiveness with other second-line treatment options, all patients who had received oxaliplatin plus fluoropyrimidines after gemcitabine-based chemotherapy were also eligible for analysis. Results: Fifty-two patients were treated with nal-IRI plus 5-FU/LV between April 2016 and August 2018. The median progression-free survival (PFS) was 3.84 months and the median overall survival (OS) was 6.79 months. Median OS from the beginning of the treatment for advanced disease was 19.9 months. Median PFS in patients that received nal-IRI plus 5-FU/LV as second-line treatment after gemcitabine-based chemotherapy was 4.49 months whereas median PFS in a matched cohort of patients treated with oxaliplatin plus fluoropyrimidines was 3.44 months (p = 0.007). Between these two groups the median OS of patients with CA 19-9 levels above the statistical median (⩾772.8 kU/l) differed significantly (9.33 versus 6.18 months, p = 0.038). Conclusion: Our data confirms the effectiveness of nal-IRI plus 5-FU/LV treatment as a well-tolerated regimen in the treatment of advanced PAC and extends available data on its use as a second-line treatment option when compared with oxaliplatin plus fluoropyrimidines.

Introduction: Vitamin D deficiency, a reversible cause of osteoporosis, is increasingly prevalent, showing varying degrees of severity that are notably pronounced among the growing population of multimorbid elderly patients. Given that the aging pancreas undergoes senescent processes leading to impaired function—which negatively impacts enteral vitamin D absorption and, consequently, elderly bone metabolism—a specific diagnostic and treatment approach is crucial. Our study aimed to determine the prevalence of vitamin D deficiency and exocrine pancreatic insufficiency (EPI) in orthogeriatric patients. We also evaluated differences in vitamin D deficiency severity between patients with normal and impaired pancreatic function. Furthermore, a short-term monitoring of vitamin D level increases after 12 days of substitution therapy in both groups aimed to inform osteoanabolic therapy for specific high-fracture-risk patients, assessing the influence of pancreatic function on substitution efficacy. Methods: We conducted a retrospective, monocentric cohort study, evaluating data from all patients hospitalized with manifest osteoporosis in an orthogeriatric department during a six-month spring/summer period. Demographic data, relevant comorbidities, the type of fracture, the amount of faecal elastase 1 (CALEX® Cap Bühlmann), and the serum levels of 25-hydroxyvitamin D (25(OH)D) were assessed. Results: We found a high prevalence (70.6%) of vitamin D deficiency (25(OH)D < 30 µg/L) among all orthogeriatric patients. Of these, 16% met the criteria for mild to severe EPI. The group with normal exocrine pancreatic function showed a higher average vitamin D value, and their increase in vitamin D levels following short-term substitution was up to 100% greater compared to the group with impaired pancreatic function. Notably, 69% of women and 20% of men met the therapeutic threshold for specific osteoanabolic osteoporosis therapy, even without a T-score. Conclusions: Our findings reveal a very high prevalence of vitamin D deficiency and a high prevalence of EPI in orthogeriatric patients. Those with impaired exocrine pancreatic function exhibit lower baseline vitamin D levels and a diminished capacity for vitamin D absorption during short-term monitoring. These results have significant clinical implications for osteoporotic therapy, given that a substantial proportion of patients, particularly women, meet the criteria for specific osteoanabolic treatment.

Late‐line treatment in metastatic colorectal cancer (mCRC) can improve prognosis. However, not every patient has a benefit and may experience severe side effects. Thus, predictive/prognostic biomarkers are urgently needed. We investigated the prognostic role of circulating tumor DNA (ctDNA) in mCRC patients before and during treatment with trifluridine/tipiracil (FTD/TPI). This noninterventional translational biomarker phase II study enrolled 30 mCRC patients (60% male, 40% female). Using a 77‐gene panel, ctDNA was detectable in 90% of patients. Tumor levels were assessed based on aneuploidy (ichorCNA) as well as the highest variant allele frequency, and correlated with overall survival (OS). Uni‐ and multivariate survival analyses were performed with clinical variables. Longitudinal changes in tumor levels over time were analyzed with linear mixed and joint models. The median OS was 8.1 months, with a recorded disease control rate of 30%. High ctDNA levels (≥ 5%) were associated with inferior survival after undergoing FTD/TPI therapy. Elevated tumor level trajectories over time were associated with higher risks of death. Therefore, ctDNA can help identify patients who are unlikely to benefit significantly from this treatment in late‐stage disease, thus preventing unnecessary treatments and their associated side effects, ultimately enhancing quality of life. The authors applied joint/mixed models that predict mortality of trifluridine/tipiracil‐treated metastatic colorectal cancer patients based on circulating tumor DNA (ctDNA) trajectories. Patients at high risk of death could be spared aggressive therapy with the prospect of a higher quality of life in their remaining lifetime, whereas patients with a good prognosis may benefit from further treatment.

The transition from hospital-based palliative care to home care is a critical phase often marked by logistical, medical, and emotional challenges. Effective discharge planning is essential to ensure continuity of care, yet gaps in communication, interdisciplinary coordination, and access to resources frequently hinder this process. This qualitative study explored key barriers, related support needs, and strategies for optimising palliative care discharge through semi-structured interviews with 28 participants, including healthcare professionals, recently discharged palliative care patients, and primary caregivers. Reflexive thematic analysis revealed five main themes: (1) discharge planning and coordination; (2) symptom management and medication; (3) psychosocial support; (4) communication and information; (5) the role of assistive devices and home care services. Discharge processes were often late or unstructured. Poor interdisciplinary collaboration and a lack of caregiver preparation also contributed to hospital readmissions and emotional distress. By focusing on needs, our analysis identifies not only what was lacking but also what is required to overcome these barriers. Our findings suggest that standardised discharge protocols and checklists, earlier planning, structured communication tools, and improved integration of home care services could enhance patient outcomes and reduce caregiver burden. Addressing psychosocial needs and ensuring timely access to assistive devices are also crucial. Strengthening interdisciplinary collaboration and refining discharge practices can facilitate smoother transitions and improve the quality of palliative care at home.

Background Nutritional factors contributing to anemia in older adults are in need of clarification. We investigated associations between nutritional biomarkers and the incidence of anemia. Methods A cross-sectional study was conducted in two centers. Data were collected from patients living in long-term care hospitals. The Geriatric Nutritional Risk Index (GNRI) was applied to determine nutritional risk. Blood parameters were obtained from medical records. Anemics vs. non-anemics were assigned according to hemoglobin levels following the WHO guidelines. Multiple linear regression analysis were performed for statistical analysis. Results The sample consisted of N  = 97 geriatric patients (mean age 84.9 years, 86% female). Anemic patients had a significantly lower GNRI ( M  = 90.6 ± 5.94; p  =.007) than non-anemic patients ( M  = 94.7 ± 6.11). Serum albumin ( p  =.008), blood iron ( p  <.001), number of erythrocytes ( p  <.001), and the hematocrit value ( p  <.001) were also significantly lower in patients with anemia. Multiple linear regression showed that serum albumin concentration, in addition to the hematocrit, was the driving factor for hemoglobin concentration in anemic patients ( p  =.004; R ²=0.77). Conclusion The present study indicates that nutritional risk plays a substantial role in anemia development in older adults. These findings may be attributable to multifactorial metabolic pathways of macro- and micronutrients on blood hemoglobin concentration. Malnourished geriatric patients with anemia may benefit from a diet rich in protein and iron-rich foods.

BackgroundTherapeutic options are limited for advanced, metastatic biliary tract cancer. The pivotal NAPOLI-1 trial demonstrated the superior clinical benefit of nanoliposomal irinotecan (Nal-IRI) in gemcitabine-pretreated patients with metastatic pancreatic ductal adenocarcinoma; however, the antitumor activity of Nal-IRI in biliary tract cancer is unknown. This is the first report describing the efficacy of Nal-IRI in biliary tract cancer.MethodsIn this multicenter retrospective cohort analysis, we identified patients with metastatic biliary tract adenocarcinoma who were treated with Nal-IRI in combination with 5-fluorouracil and folinic acid following tumor progression under standard therapy at one of the study centers between May 2016 and January 2019. We assessed disease control rate (DCR), progression-free survival (PFS), and overall survival (OS).ResultsThere were 14 patients; the median age at the time of diagnosis and the median age at the initiation of Nal-IRI were 59.3 and 60.0 years, respectively. Nal-IRI in combination with 5-fluorouracil and folinic acid was administered as second-, third-, fourth-, and fifth-line treatment in 6 (43%), 5 (36%), 2 (14%), and 1 (7%) patient with metastatic disease, respectively. The objective DCR with Nal-IRI was 50% (7/14 patients). Six patients (43%) had partial response, and one patient (7%) had stable disease. Progressive disease was observed in seven patients. The median PFS and median OS following Nal-IRI initiation were 10.6 and 24.1 months, respectively.ConclusionsThis retrospective analysis provides the first evidence that Nal-IRI might exhibit a clinical meaningful antitumor activity in metastatic biliary tract cancer.

Introduction Symptoms of cancer‐related fatigue (CRF) can have a significant impact on patients' quality of life and treatment adherence. We aimed to investigate the relationship between CRF and multiple psychosocial and somatic indicators within a large mixed cancer sample. Methods In this cross‐sectional study, N = 1787 outpatients with cancer were assessed for CRF, pain, anxiety, and depression using validated screening instruments. We further obtained clinical parameters (Hb, CRP, creatinine, leukocytes, ASAT, and ALAT), sociodemographic data (age, gender, income, education level, marital status, parenthood, and living area), and lifestyle factors. Multivariate linear regression models were applied to estimate the impact of each indicator on CRF. Results Overall, 90.6% of patients experienced some CRF, with 14.8% experiencing severe CRF. No gender difference was found in the prevalence of CRF. Patients with higher levels of pain, depressive symptoms, and lower Hb levels had significantly higher levels of CRF (ps <0.001). Lower levels of CRF were observed in patients who had children (p = 0.03), had less education (p < 0.001), and were physically active for more than 2 h per week before their oncological diagnosis (p = 0.014). The latter was only a significant indicator in the male subsample. Conclusion The present results demonstrate a high prevalence of CRF and highlight that not only somatic and psychosocial factors, but also lifestyle factors prior to diagnosis appear to be associated with the etiology and persistence of CRF. To effectively treat CRF, a biopsychosocial, personalized approach is recommended.

Background: Targeted therapies offer novel opportunities to explore biomarkers based on their mode of action. Taking this into consideration, we evaluated six angiogenesis-related proteins as potential predictive biomarkers, which expression might predict the benefit of bevacizumab treatment in patients with metastatic colorectal cancer (mCRC). Methods: This was a phase II multicenter, two-armed, randomized study, in which patients with mCRC were treated with XELIRI (capecitabine and irinotecan) plus bevacizumab followed by XELOX (capecitabine and oxaliplatin) plus bevacizumab (Arm A) or the reverse sequence (Arm B). Tissue expression level of six prespecified candidates [microvessel density assessed by CD31, PTEN, αV integrin, CD98hc, uPAR and NRP-1] was analyzed via immunohistochemistry. The prognostic impact on survival was quantified using the Cox regression model. The predictive potential for benefit from Arm A versus Arm B treatment was investigated by fitting an interaction between the biomarkers and treatment assignment within a multivariable Cox model. Results: In total, 74 out of 126 patients were included in the analysis. The expression of PTEN, αV integrin, uPAR and NRP-1 was not associated with progression-free survival (PFS) or overall survival (OS). For the first time, we identified that patients with tumors expressing CD98hc had a longer PFS than patients without CD98hc-expression (p = 0.032). More importantly, and in accordance with previous studies, low microvessel density was found to be associated with a reduced PFS [adjusted HR per doubling of CD31-expression (p = 0.53, 95% confidence interval: 0.30–0.95, p = 0.034)]. Conclusions: These results can contribute to the development of a personalized strategy for the treatment of mCRC with bevacizumab.

ABSTRACT Introduction People with intellectual disabilities (ID) face significant barriers to healthcare and preventive cancer care, resulting in delayed cancer diagnosis and higher mortality rates. There is limited understanding of the factors that influence their participation in colorectal cancer (CRC) screening, particularly from their own perspectives. This study aimed to identify the barriers, facilitators, and needs of people with ID for an inclusive CRC screening programme from their own experiences and viewpoints. Methods Semi‐structured qualitative interviews and focus groups (N = 31) were conducted with adults with ID in Austria. Interviews and group discussions were audio recorded and transcribed verbatim. Thematic analysis was used as a flexible method to analyse the data. Results Five themes were identified from the data with each consisting of two to four sub‐themes: (1) independence within individually adjusted scopes of arrangement and decision‐making, (2) ‘When it comes to health, I do it’, (3) enhancing wellbeing, (4) seeing the person first, then their ID, and (5) deficits in resources and the healthcare system. Conclusion The findings reveal significant barriers to healthcare and preventive cancer care for people with ID. The following practical implications were derived: Eliminating discrimination, improving accessibility, designing appropriate information and educational materials, implementing mandatory ID‐specific training for health professionals, considering the importance of emotions and implementing ID‐appropriate health services. Considering these aspects when developing inclusive cancer screening programmes is of paramount importance to promote equitable health and cancer prevention, especially for marginalised and vulnerable groups.