Search Results (22)

Neuroendocrine neoplasms (NENs) are rare and heterogeneous tumors with heterogeneity in morphology and molecular profile and consequently resulting in a heterogeneous biological behavior. They have a more indolent natural history compared to the classic cancer and may emerge in any site of the human body, but usually they have gastroenteropancreatic (GEP) or bronchopulmonary (BP) origin. When NENs are well differentiated, they are called neuroendocrine tumors (NETs) as opposed to poorly differentiated neuroendocrine carcinomas (NECs). They may secrete a bioactive molecule resulting in a secretory syndrome or they may not be associated with any secretory product, defining functional and non-functional NENs. The hormonal hypersecretion syndromes, the chronic symptom burden, the tumor-related inflammation, and the treatment side effects impair nutritional intake and absorption while increasing metabolic needs. The present comprehensive narrative review is summarizing established and emerging methods of nutritional and body composition assessment, and the recent evidence of interventions for sarcopenia and malnutrition in patients with NETs. Early identification and management of malnutrition and sarcopenia are fundamental steps to improve quality of life and clinical outcomes in these patients during the long natural history of these neoplasms. Full article

Objectives: The aim of our study is to evaluate whether texture analysis of 68Ga-DOTATOC PET/CT images can predict clinical outcome in patients with neuroendocrine tumors (NET). Methods: Forty-seven NET patients who had undergone 68Ga-DOTATOC PET/CT were studied. Primary tumors were localized in the gastroenteropancreatic (n = 35), bronchopulmonary (n = 8), and other (n = 4) districts. NET lesions were segmented using an automated contouring program and subjected to texture analysis, thus obtaining the conventional parameters SUVmax and SUVmean, volumetric parameters of the primary lesion, such as Receptor-Expressing Tumor Volume (RETV) and Total Lesion Receptor Expression (TLRE), volumetric parameters of the lesions in the whole-body, such as wbRETV and wbTLRE, and texture features such as Coefficient of Variation (CoV), HISTO Skewness, HISTO Kurtosis, HISTO Entropy-log₁₀, GLCM Entropy-log₁₀, GLCM Dissimilarity, and NGLDM Coarseness. Patients were subjected to a mean follow-up period of 17 months, and survival analysis was performed using the Kaplan–Meier method and log-rank tests. Results: Forty-seven primary lesions were analyzed. Survival analysis was performed, including clinical variables along with conventional, volumetric, and texture imaging features. At univariate analysis, overall survival (OS) was predicted by age (p = 0.0079), grading (p = 0.0130), SUVmax (p = 0.0017), SUVmean (p = 0.0011), CoV (p = 0.0037), HISTO Entropy-log₁₀ (p = 0.0039), GLCM Entropy-log₁₀ (p = 0.0044), and GLCM Dissimilarity (p = 0.0063). At multivariate analysis, only GLCM Entropy-log₁₀ was retained in the model (χ² = 7.7120, p = 0.0055). Kaplan–Meier curves showed that patients with GLCM Entropy-log₁₀ >1.28 had a significantly better OS than patients with GLCM Entropy-log₁₀ ≤1.28 (χ² = 10.6063, p = 0.0011). Conclusions: Texture analysis of 68Ga-DOTATOC PET/CT images, by revealing the heterogeneity of somatostatin receptor expression, can predict the clinical outcome of NET patients. Full article

Neuroendocrine neoplasms (NENs) comprise a heterogeneous tumor group arising from neuroendocrine cells, commonly originating in the gastroenteropancreatic tract and bronchopulmonary system. Their incidence has risen significantly, owing to improved diagnostic techniques and increased clinical recognition. While previous reviews have explored the molecular and genetic basis of NENs, limited attention has been given to the role of epigenetic modifications, particularly DNA methylation, in tumorigenesis and disease progression. This review focuses on lung, pancreas, and thyroid well-differentiated neuroendocrine tumors (NETs), highlighting epigenetic mechanisms, particularly DNA methylation, as promising biomarkers for early diagnosis and risk stratification. Aberrant DNA methylation can silence key tumor suppressor genes, including RASSF1A and CDKN2A, thereby promoting tumorigenesis. Integrating DNA methylation profiles with conventional biomarkers such as chromogranin A (CgA) may enhance diagnostic accuracy and inform therapeutic strategies. Emerging epigenetic therapies offer potential avenues for personalized treatment based on molecular profiling. Unlike prior reviews that broadly cover genetic and epigenetic changes in NENs, this review uniquely emphasizes the translational potential of epigenetic biomarkers in clinical practice. By synthesizing recent findings and evaluating their clinical implications, we aim to bridge the gap between molecular research and practical applications in diagnosis, prognosis, and therapy. Full article

Introduction: Neuroendocrine tumors are a diverse group of tumors predominantly found in the gastrointestinal tract or respiratory system. Methods: This retrospective study aimed to measure the serum concentrations of LRP6 (low-density lipoprotein receptor-related protein 6), SFRP3 (secreted frizzled-related protein 3), and DVL1 (segment polarity protein dishevelled homolog) using the ELISA method in patients with NETs (N = 80) and a control group (N = 62). We evaluated the results against various demographic, clinicopathological, and biochemical characteristics. Results: Our analyses revealed that the concentration of SFRP3 in patients with neuroendocrine tumors was significantly elevated (p < 0.001) compared to the control group. Additionally, DVL1 concentrations were significantly higher (p < 0.01) in patients with BP-NETs compared to GEP-NETs. Furthermore, DVL1 analysis showed a moderate negative correlation with chromogranin A (p < 0.001) and weak negative correlations with serotonin (p < 0.05) and 5-HIAA (p < 0.05). Significant negative correlations were also observed between DVL1 and age in the control group (p < 0.01), and between LRP6 and Ki-67 in the study group. Conclusions: These results suggest that changes in the SFRP3 and DVL1 pathways play a key role in NET development. Elevated levels of these proteins highlight their importance in tumor biology, with SFRP3 and DVL1 potentially being crucial in NET molecular mechanisms. Further research is needed to explore their roles and potential in diagnosis and treatment. Full article

Background: Malignant tumors represent a significant pathology with a profound global impact on the medical system. The fight against cancer represents a significant challenge, with multidisciplinary teams identifying numerous areas requiring improvement to enhance the prognosis. Facilitating the patient’s journey from diagnosis to treatment represents one such area of concern. One area of research interest is the use of various biomarkers to accurately predict the outcome of these patients. A substantial body of research has been conducted over the years examining the relationship between C-reactive protein (CRP) and malignant tumors. The existing literature suggests that combining imaging diagnostic modalities with biomarkers, such as CRP, may enhance diagnostic accuracy. Methods: A systematic review was conducted on the PubMed and Web of Science platforms with the objective of documenting the interrelationship between CRP value and tumor grading for malignant tumors. After the application of the exclusion and inclusion criteria, 17 studies were identified, published between 2002 and 2024, comprising a total of 9727 patients. Results: These studies indicate this interrelationship for soft tissue sarcomas and for renal, colorectal, esophageal, pancreatic, brain, bronchopulmonary, ovarian, and mesenchymal tumors. Conclusions: Elevated CRP levels are correlated with higher grading, thereby underscoring the potential utility of this biomarker in clinical prognostication. Full article

Neuroendocrine tumors (NETs) are a heterogeneous group of tumors that are characteristically different from other malignancies. The difference is not only in the prognosis, which is usually more favorable in such patients, but also in the high clinical progression of the disease, where NET patients do not experience the cachexia typical of other malignancies. The purposes of this study were to evaluate the ghrelin and leptin levels in a group of patients diagnosed with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) and bronchopulmonary neuroendocrine tumors (BP-NETs) and to analyze the relationship between the body mass index (BMI), cachexia and selected NET markers. The study group comprised 52 patients with GEP-NETs and BP-NETs, while the controls comprised 67 healthy volunteers. The ghrelin and leptin concentrations were determined in both groups. The concentrations of chromogranin A, serotonin, 5-hydroxyindoleacetic acid (5-HIAA), total cholesterol, triglycerides and glucose were determined in the study group. Characteristics of the study group and of the controls were defined by age, sex and BMI, and the effects of these factors on the ghrelin and leptin concentrations were assessed. The data obtained were subject to statistical analysis. The study cohort showed higher levels of ghrelin as compared to the controls (142.31 ± 26.00 vs. 121.49 ± 35.45, p = 0.016), and no statistical difference in the levels of leptin (11.15 ± 9.6 vs. 12.94 ± 20.30, p = 0.439) were observed. Significantly lower levels of leptin were found in patients with the small intestine primary location, as compared to individuals with primary locations in the lungs and the pancreas (4.9 ± 6.49 vs. 16.97 ± 15.76, p = 0.045, and 4.9 ± 6.49 vs. 12.89 ± 8.56, p = 0.016, respectively). A positive correlation was observed between the leptin levels and the BMIs in both the study group (r_S = 0.33, p = 0.016) and the controls (r_S = 0.41, p = 0.001). The study group showed a negative correlation between the leptin levels and 5-HIAA (r_S = −0.32, p = 0.026) and a negative correlation between the leptin levels and Ki-67 (r_S = −0.33, p = 0.018). The control group showed negative correlations between the ghrelin and the volunteer age (r_S = −0.41, p = 0.008), the leptin and the volunteer age (r_S = −0.44, p < 0.001), the leptin and total cholesterol (r_S = −0.24, p < 0.049) as well as the leptin and triglycerides (r_S = −0.33, p < 0.006). The current study emphasized the importance of the markers’ determination, where ghrelin appears as a valuable diagnostic biomarker in NETs, probably responsible for maintaining a normal BMI, despite the progression of the disease. Full article

As cancer progresses, patients may experience physical decline, which can impair their ability to carry out essential daily tasks. The aim of this study was to analyze the levels of physical activity in patients with advanced cancer undergoing systemic treatment and its relationship with sociodemographic, clinical, and psychological factors. A prospective, cross-sectional, multicenter study was carried out in 15 oncology departments in Spain. Patients with locally advanced, unresectable, or metastatic cancer who were candidates for systemic treatment were included. Participants completed demographic information and psychological scales. In total, 508 patients were included in the study, the majority of whom were male, over the age of 65, and diagnosed with bronchopulmonary tumors (36%) and metastatic disease. Based on their physical activity levels, participants were categorized as sedentary (20%, n = 190), engaging in light physical activity (43%, n = 412), or demonstrating moderate physical activity (37%, n = 351). Patients who were over 65 years old; had a worse baseline status (ECOG ≥ 1); lacked a partner; had a lower educational level; or were retired or unemployed were found to have lower levels of physical activity. Those with sedentary physical activity reported higher levels of psychological distress, anxiety, depression, somatization, and physical symptoms, as well as worse functional status, global health status, and well-being. Understanding the complex interplay between physical activity and sociodemographic, clinical, and psychological factors can help neuroscientists develop tailored exercise interventions that address the unique needs of advanced cancer patients. Full article

There are several well-described molecular mechanisms that influence cell growth and are related to the development of cancer. Chemokines constitute a fundamental element that is not only involved in local growth but also affects angiogenesis, tumor spread, and metastatic disease. Among them, the C-X-C motif chemokine ligand 12 (CXCL12) and its specific receptor the chemokine C-X-C motif receptor 4 (CXCR4) have been widely studied. The overexpression in cell membranes of CXCR4 has been shown to be associated with the development of different kinds of histological malignancies, such as adenocarcinomas, epidermoid carcinomas, mesenchymal tumors, or neuroendocrine neoplasms (NENs). The molecular synapsis between CXCL12 and CXCR4 leads to the interaction of G proteins and the activation of different intracellular signaling pathways in both gastroenteropancreatic (GEP) and bronchopulmonary (BP) NENs, conferring greater capacity for locoregional aggressiveness, the epithelial–mesenchymal transition (EMT), and the appearance of metastases. Therefore, it has been hypothesized as to how to design tools that target this receptor. The aim of this review is to focus on current knowledge of the relationship between CXCR4 and NENs, with a special emphasis on diagnostic and therapeutic molecular targets. Full article

Aspergillosis is a fungal infection caused by various species of Aspergillus, most notably A. fumigatus. This fungus causes a spectrum of diseases, including allergic bronchopulmonary aspergillosis, aspergilloma, chronic pulmonary aspergillosis, and invasive aspergillosis. The clinical manifestations and severity of aspergillosis can vary depending on individual immune status and the specific species of Aspergillus involved. The recognition of Aspergillus involves pathogen-associated molecular patterns (PAMPs) such as glucan, galactomannan, mannose, and conidial surface proteins. These are recognized by the pathogen recognition receptors present on immune cells such as Toll-like receptors (TLR-1,2,3,4, etc.) and C-type lectins (Dectin-1 and Dectin-2). We discuss the roles of cytokines and pathogen recognition in aspergillosis from both the perspective of human and experimental infection. Several cytokines and chemokines have been implicated in the immune response to Aspergillus infection, including interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), CCR4, CCR17, and other interleukins. For example, allergic bronchopulmonary aspergillosis (ABPA) is characterized by Th2 and Th9 cell-type immunity and involves interleukin (IL)-4, IL-5, IL-13, and IL-10. In contrast, it has been observed that invasive aspergillosis involves Th1 and Th17 cell-type immunity via IFN-γ, IL-1, IL-6, and IL-17. These cytokines activate various immune cells and stimulate the production of other immune molecules, such as antimicrobial peptides and reactive oxygen species, which aid in the clearance of the fungal pathogen. Moreover, they help to initiate and coordinate the immune response, recruit immune cells to the site of infection, and promote clearance of the fungus. Insight into the host response from both human and animal studies may aid in understanding the immune response in aspergillosis, possibly leading to harnessing the power of cytokines or cytokine (receptor) antagonists and transforming them into precise immunotherapeutic strategies. This could advance personalized medicine. Full article

Bronchopulmonary cancer is the leading cause of cancer deaths globally. Rheumatoid arthritis is one of the risk factors for lung cancer, and those who use methotrexate have a higher risk of developing lung cancer. We present the case of an 80-year-old patient who is a former smoker and is known to have rheumatoid arthritis, being treated using methotrexate; they were brought by ambulance to the emergency room for coughing with ineffective expectoration, dyspnea on slight exertion, and right-lateral chest pain with onset about one month prior and progressive worsening. Imaging showed a 7 cm/6 cm LID tumorous lung formation with parietal invasion and C7 rib lysis, as well as diffuse fibrotic interstitial changes predominantly in the lower lobes. An ultrasound-guided transthoracic lung biopsy was performed, and histopathological examination established the diagnosis of invasive squamous cell lung carcinoma, G2. In conclusion, the chest pain interpreted by the patient as rheumatic pain delayed the diagnosis of lung cancer; the patient presented rather late to the hospital once respiratory failure set in. Full article

The purpose of the study was to identify subgroups of advanced cancer patients who experienced grade 3–4 toxicities as reported by their oncologists as well as identify the demographic, clinical, and treatment symptom characteristics as well as QoL outcomes associated with distinct profiles of each patient. A prospective, multicenter, observational study was conducted with advanced cancer patients of 15 different hospitals across Spain. After three months of systemic cancer treatment, participants completed questionnaires that evaluated psychological distress (BSI-18), quality of life (EORTC QLQ-C30) and fatigue (FAS). The most common tumor sites for the 557 cancer patients with a mean age of 65 years were bronchopulmonary, digestive, and pancreas. Overall, 19% of patients experienced high-grade toxicities (grade 3–4) during treatment. Patients with recurrent advanced cancer, with non-adenocarcinoma cancer, undergoing chemotherapy, and a showing deteriorated baseline status (ECOG > 1) were more likely to experience higher toxicity. Patients who experienced grade 3–4 toxicities during cancer treatment had their treatment suspended in 59% of the cases. Additionally, 87% of the patients had a dose adjustment or a cycle delayed in their treatment due to a high risk of dying during treatment. Future research should focus on identifying interventions to reduce high-grade toxicities and improve quality of life in cancer patients. Full article

Background: Neuroendocrine tumors (NET) are a rare group of epithelial neoplasms present in the gastrointestinal tract (GI) (67.5%) and bronchopulmonary tree (25.3–30%), and in 15% of cases, their primary sites cannot be identified. Although endoscopic screening, improvements in pathological techniques, and early detection have shown improvements in NET survival rates, the prognosis of advanced, metastatic, and poorly differentiated NET is very poor. In this study, we aimed to evaluate the effect of gastrointestinal and pancreatic (GEPs) NETs’ grade on overall survival. Method: We searched observational studies describing the overall survival or prognostic factors of primary GEP NETs from May 2011–May 2021 following the PRISMA guidelines. Studies describing the effect of primary grade 3 GEP NETs on overall survival were included. A meta-analysis was performed, and a pooled hazard ratio and their 95% confidence interval (95% CI) were obtained. Forest plots were created using random effects models and a sensitivity analysis was performed to account for the heterogeneity. Results: Seven studies with 7692 confirmed patients were included. In our meta-analysis, grade 3 GEP NETs were associated with higher odds of poor survival (pooled HR: 2.73; 95% CI: 1.36–5.47; p = 0.005), with a 92% heterogeneity between studies (p < 0.0001). To account for this heterogeneity, a sensitivity analysis was performed by removing two outlying studies (Fathi et al. and Foubert et al.) on funnel plots. The results after the sensitivity analysis did not change and still showed a significant association of grade 3 with a poor survival (pooled HR: 4.53; 95% CI: 3.54–5.78; p < 0.00001), with no heterogeneity between studies (p = 0.72; I² = 0%). Conclusions: Our meta-analysis found that grade 3 GEP NETs are associated with poor survival and additional future studies are needed to identify other risk factors associated with poor survival in GEP NETs to improve their mortality. Full article

Lung cancer is the leading cause of cancer-related deaths worldwide. This study aimed to compare the bronchial microbiota of patients with lung cancer and patients with benign pulmonary diseases undergoing bronchoscopy, and to assess the stress levels associated with invasive diagnostic lung tests. A cross-sectional study was conducted at the “Victor Babes” Hospital for Infectious Diseases and Pulmonology in Timisoara, Romania. A total of 33 patients with histologically diagnosed bronchopulmonary cancer and 33 control patients with benign lung pathologies underwent bronchoscopy. Bronchial microbiota was analyzed by multiplex PCR, culture media, and cytology. Anxiety and depression levels were assessed using the ECOG performance status scale, Karnofsky scale, GAD-7, PHQ-9, and HADS questionnaires. There were no significant differences in the presence of common microbial species between the two groups, except for Acinetobacter spp. Which was identified in 15.2% of patients with lung cancer and 0.0% in the control group, Candida spp. Was more prevalent in the benign group (24.2% vs. 6.1%), and the Parainfluenza virus was detected only in the malignant group (21.1% vs. 0.0%). Cytology results showed a higher prevalence of atypical and tumoral cells in the malignant group (39.4% and 30.0%, respectively), as well as higher lymphocyte levels in the benign group (69.7% vs. 24.2%). Patients with lung cancer had significantly lower performance status on the ECOG scale (2.34 vs. 1.92), lower Karnofsky scores (71.36 vs. 79.43), and higher GAD-7 and PHQ-9 scores at the initial evaluation compared to the benign group. At the 90-day follow-up, ECOG and Karnofsky scores remained significantly different from the initial evaluation, but only GAD-7 scores showed a significant difference between the two groups. There were differences in the bronchial microbiota between patients with lung cancer and benign pulmonary diseases, with a higher prevalence of Candida spp. in the benign group and exclusive detection of Acinetobacter spp. and Parainfluenza virus in the malignant group. Patients with lung cancer exhibited higher stress levels, more severe anxiety, and depression symptoms, which persisted during follow-up. Further research is needed to understand the role of bronchial microbiota in lung cancer and the impact of stress on patient outcomes. Full article

There is a lack of effective biomarkers for diagnosing lung neuroendocrine neoplasms (LNENs). A known small cell lung cancer (SCLC) biomarker is a pro-gastrin-releasing peptide (ProGRP), but not for all LNENs, especially for bronchopulmonary carcinoids. This study aimed to evaluate the diagnostic value of ProGRP and chromogranin A (CgA) in diagnosing LNENs. The ProGRP and CgA levels in 290 cases of LNENs and 54 healthy controls (HCs) were measured. The median ProGRP concentration in the group of LNEN patients was 136.4 pg/mL, higher than that of HCs at 6.5 pg/mL. Most of the LNEN cohort was well-differentiated tumors (typical and atypical carcinoids, n = 262, 91.7% of all LNENs). The sensitivity, specificity, and area under the curve (AUC) of ProGRP when distinguishing LNENs vs. HCs were 94.8%, 100%, and 0.995. CgA (AUC = 0.375) could not determine LNENs vs. HCs. Therefore, based on these results, ProGRP may be considered as an effective marker for diagnosing LNENs. Full article

The therapeutic alliance is an important factor in successful cancer treatment, particularly for those with advanced cancer. This study aims to determine how the therapeutic alliance relates to prognostic preferences and satisfaction with the physician and medical care among patients with advanced cancer. We conducted a cross-sectional study to explore the therapeutic relationship, trust, satisfaction with healthcare, and prognostic preferences among 946 patients with advanced cancer at 15 tertiary hospitals in Spain. Participants completed questionnaires with self-reported measures. Most were male, aged > 65 years, with bronchopulmonary (29%) or colorectal (16%) tumors and metastatic disease at diagnosis. Results revealed that 84% of patients had a good therapeutic alliance. Collaborative and affective bond was positively associated with a preference to know the prognosis and satisfaction with care and decision. There was no difference in a therapeutic alliance based on clinical or sociodemographic factors. The therapeutic alliance between patient and physician is essential for successful treatment outcomes and better overall satisfaction. Therefore, it is vital for healthcare providers to focus on establishing and maintaining a strong relationship with their patients. To achieve this, transparency and care should be prioritized, as well as respect for the preferences of patients regarding the prognosis of their illness. Full article