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14 pages, 2501 KiB  
Article
Therapeutic Patterns and Surgical Decision-Making in Breast Cancer: A Retrospective Regional Cohort Study in Romania
by Ramona Andreea Cioroianu, Michael Schenker, Virginia-Maria Rădulescu, Tradian Ciprian Berisha, George Ovidiu Cioroianu, Mihaela Popescu, Cristina Mihaela Ciofiac, Ana Maria Petrescu and Stelian Ștefăniță Mogoantă
Clin. Pract. 2025, 15(8), 145; https://doi.org/10.3390/clinpract15080145 - 5 Aug 2025
Abstract
Background: Breast cancer is the most prevalent malignancy among women globally. In Romania, it is the most frequent form of cancer affecting women, with approximately 12,000 new cases diagnosed annually, and the second most common cause of cancer-related mortality, second only to [...] Read more.
Background: Breast cancer is the most prevalent malignancy among women globally. In Romania, it is the most frequent form of cancer affecting women, with approximately 12,000 new cases diagnosed annually, and the second most common cause of cancer-related mortality, second only to lung cancer. Methods: This study looked at 79 breast cancer patients from Oltenia, concentrating on epidemiology, histology, diagnostic features, and treatments. Patients were chosen based on inclusion criteria such as histopathologically verified diagnosis, availability of clinical and treatment data, and follow-up information. The analyzed biological material consisted of tissue samples taken from the breast parenchyma and axillary lymph nodes. Even though not the primary subject of this paper, all patients underwent immunohistochemical (IHC) evaluation both preoperatively and postoperatively. Results: We found invasive ductal carcinoma to be the predominant type, while ductal carcinoma in situ (DCIS) and mixed types were rare. We performed cross-tabulations of metastasis versus nodal status and age versus therapy type; none reached significance (all p > 0.05), suggesting observed differences were likely due to chance. A chi-square test comparing surgical interventions (breast-conserving vs. mastectomy) in patients who did or did not receive chemotherapy showed, χ2 = 3.17, p = 0.367, indicating that chemotherapy did not significantly influence surgical choice. Importantly, adjuvant chemotherapy and radiotherapy were used at similar rates across age groups, whereas neoadjuvant hormonal (endocrine) therapy was more common in older patients (but without statistical significance). Conclusions: Finally, we discussed the consequences of individualized care and early detection. Romania’s shockingly low screening rate, which contributes to delayed diagnosis, emphasizes the importance of improved population medical examination and tailored treatment options. Also, the country has one of the lowest rates of mammography uptake in Europe and no systematic population screening program. Full article
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10 pages, 459 KiB  
Article
Influence of Primary Care Physicians on End-of-Life Treatment Choices in Lung Cancer Diagnosed in the Emergency Department
by Tatsuyuki Kawahara, Nobuaki Ochi, Hirohito Kirishi, Yusuke Sunada, Ayaka Mimura, Naruhiko Ichiyama, Yoko Kosaka, Yasunari Nagasaki, Hidekazu Nakanishi, Hiromichi Yamane and Nagio Takigawa
J. Pers. Med. 2025, 15(8), 339; https://doi.org/10.3390/jpm15080339 - 1 Aug 2025
Viewed by 150
Abstract
Background: Lung cancer remains one of the leading causes of cancer-related mortality worldwide. While most diagnoses occur in outpatient settings, a subset of cases are incidentally identified during emergency department (ED) visits. The clinical characteristics and treatment decisions of these patients, particularly [...] Read more.
Background: Lung cancer remains one of the leading causes of cancer-related mortality worldwide. While most diagnoses occur in outpatient settings, a subset of cases are incidentally identified during emergency department (ED) visits. The clinical characteristics and treatment decisions of these patients, particularly in relation to social background factors such as living situation and access to primary care, remain poorly understood. Methods: We conducted a retrospective study of patients diagnosed with malignancies in the ED of a single institution between April 2018 and December 2021. Patients diagnosed with lung cancer within 60 days of an ED visit were included. Data on demographics, disease status, treatment decisions, and background factors—including whether patients lived alone or had a primary care physician (PCP)—were extracted and analyzed. Results: Among 32,108 patients who visited the ED, 148 were diagnosed with malignancy within 60 days; 23 had lung cancer. Of these, 69.6% had metastatic disease at diagnosis, and 60.9% received active treatment (surgery or chemotherapy). No significant associations were observed between the extent of disease and either living arrangement or PCP status. However, the presence of a PCP was significantly associated with the selection of best supportive care (p = 0.023). No significant difference in treatment decisions was observed based on age (cutoff: 75 years). Conclusions: Although social background factors such as living alone were not significantly associated with cancer stage or treatment choice, the presence of a primary care physician was associated with a higher likelihood of best supportive care being selected. This may indicate that patients with an established PCP have more clearly defined care goals at the end of life. These findings suggest that primary care access may play a role in shaping end-of-life care preferences, highlighting the importance of personalized approaches in acute oncology care. Full article
(This article belongs to the Special Issue New Insights into Personalized Care in Advance Care Planning)
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20 pages, 12367 KiB  
Article
Chemosensitizer Effects of Cisplatin- and 5-Fluorouracil-Treated Hepatocellular Carcinomas by Lidocaine
by Teng-Wei Chen, Hsiu-Lung Fan, Shu-Ting Liu and Shih-Ming Huang
Int. J. Mol. Sci. 2025, 26(15), 7137; https://doi.org/10.3390/ijms26157137 - 24 Jul 2025
Viewed by 275
Abstract
Approximately 90% of liver cancer cases are classified as hepatocellular carcinomas (HCCs), with chemotherapy and immunotherapy being the most recommended treatment options. While conventional chemotherapy specifically targets rapidly dividing cancer cells, it can also impact on healthy cells that are proliferating quickly. This [...] Read more.
Approximately 90% of liver cancer cases are classified as hepatocellular carcinomas (HCCs), with chemotherapy and immunotherapy being the most recommended treatment options. While conventional chemotherapy specifically targets rapidly dividing cancer cells, it can also impact on healthy cells that are proliferating quickly. This collateral damage to healthy cells, along with the potential for cancer cells to develop resistance, presents significant challenges for conventional chemotherapy in liver cancer patients. Hepatic artery infusion of chemotherapy (HAIC) generally leads to reduced toxicity and fewer side effects. The process of catheter insertion is usually performed under local anesthesia, with lidocaine being the preferred choice to combine with various chemotherapeutics in HCC treatment. In our study, we explored the effects of repurposing lidocaine in combination with cisplatin or 5-fluorouracil (5-FU) on two HCC cell lines, HepG2 and Hep3B. Our cytotoxicity analysis revealed that lidocaine functions as a chemosensitizer for cisplatin and 5-FU in both HepG2 and Hep3B cells. Specifically, we observed an increase in the subG1 population and a reduction in cytosolic reactive oxygen species in cisplatin- or 5-FU-treated HepG2 and Hep3B cells. Interestingly, lidocaine selectively decreased the reduced/oxidized glutathione ratio in cisplatin- or 5-FU-treated HepG2 cells but not in Hep3B cells. Furthermore, lidocaine induced endoplasmic reticulum stress, apoptosis, mitochondrial membrane depolarization, lipid peroxidation, and autophagy while suppressing cellular proliferation HepG2 and Hep3B cells. In conclusion, our study demonstrates the synergistic potential of combining lidocaine with cisplatin or 5-FU for the treatment of HCC, indicating that lidocaine may serve as an effective chemosensitizer. These findings highlight a new clinical advantage of using repurposing lidocaine as a chemosensitizer in the current HAIC procedure, suggesting that this combination warrants further exploration through rigorous clinical trials. In the future, we can better optimize therapeutic regimens, potentially leading to improved patient outcomes in HCCs. Full article
(This article belongs to the Special Issue Current Research on Cancer Biology and Therapeutics: Third Edition)
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15 pages, 1272 KiB  
Article
Gender Differences in Knowledge and Attitudes on Hematopoietic Stem Cell Donation Among Apulian Citizens: An Explorative Study
by Elsa Vitale, Roberto Lupo, Stefano Botti, Chiara Ianne, Alessia Lezzi, Giorgio De Nunzio, Donato Cascio, Ivan Rubbi, Simone Zacchino, Gianandrea Pasquinelli, Doria Valentini, Valeria Soffientini, Valentina De Cecco, Chiara Cannici, Marco Cioce and Luana Conte
Hemato 2025, 6(3), 24; https://doi.org/10.3390/hemato6030024 - 22 Jul 2025
Viewed by 236
Abstract
Background: It is estimated that in Italy, there were 364,000 new diagnoses of neoplasms each year and that the overall incidence of blood cancers was 10% of these. Leukemia and lymphomas represented the ninth and eighth places, respectively, among the causes of death [...] Read more.
Background: It is estimated that in Italy, there were 364,000 new diagnoses of neoplasms each year and that the overall incidence of blood cancers was 10% of these. Leukemia and lymphomas represented the ninth and eighth places, respectively, among the causes of death from neoplasia. Hematopoietic stem cell transplantation represented an effective treatment option for many of these malignancies, and not only that: benign and congenital diseases could also be treated. Objective: To assess knowledge among the Apulian population regarding stem cell donation and factors that could influence this choice, focusing especially on the knowledge of the residents of Puglia, Italy on how stem cells were harvested and their functions, their reasons for joining the National Registry, and the reasons that hold them back from making such a choice. Study Design: An observational and cross-sectional study was conducted, through snowball sampling methodology, until data saturation. An online survey was conducted, which included several Italian associations. The questionnaire administered contained five main sections, such as sociodemographic data, knowledge of the existence of National Registries and their adherence, the nationwide presence of various associations that promote donation, knowledge with respect to the structure, use and functions of stem cells, sources of procurement, such as bone marrow, peripheral blood and umbilical cord, and related procedures, beliefs, attitudes, values, and opinions of the Italian population regarding the topic, and degree of information and education regarding bone marrow donation. Results: A total of 567 Apulian citizens were enrolled. Of these, 75.3% were female and 96.8% were aged between 18 and 65 years. Most of participants were single (46.9%) and married (47.3%) and had a diploma (44.4%), and less had a degree (35.8%). Significant differences were recorded between gender, singles, and married participants, and participants with a diploma or a degree and the items proposed. Conclusions: A true culture of donation in our region was not clearly spread. Although something has been accomplished in recent years in terms of deceased donor donation, still a great deal needs to be achieved for living donation, which encountered a great deal of resistance. It has been deemed necessary to seek winning solutions to this issue in terms of communication and information campaigns, raising awareness and empowering citizens to express consciously their concerns about organs and tissues and to stand in solidarity with those who suffered. Full article
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32 pages, 3198 KiB  
Review
Shining the Path of Precision Diagnostic: Advancements in Photonic Sensors for Liquid Biopsy
by Paola Colapietro, Giuseppe Brunetti, Carlotta Panciera, Aurora Elicio and Caterina Ciminelli
Biosensors 2025, 15(8), 473; https://doi.org/10.3390/bios15080473 - 22 Jul 2025
Viewed by 326
Abstract
Liquid biopsy (LB) has gained attention as a valuable approach for cancer diagnostics, providing a minimally invasive option compared to conventional tissue biopsies and helping to overcome issues related to patient discomfort and procedural invasiveness. Recent advances in biosensor technologies, particularly photonic sensors, [...] Read more.
Liquid biopsy (LB) has gained attention as a valuable approach for cancer diagnostics, providing a minimally invasive option compared to conventional tissue biopsies and helping to overcome issues related to patient discomfort and procedural invasiveness. Recent advances in biosensor technologies, particularly photonic sensors, have improved the accuracy, speed, and real-time capabilities for detecting circulating biomarkers in biological fluids. Incorporating these tools into clinical practice facilitates more informed therapeutic choices and contributes to tailoring treatments to individual patient profiles. This review highlights the clinical potential of LB, examines technological limitations, and outlines future research directions. Departing from traditional biosensor focused reviews, it adopts a reverse-mapping approach grounded in clinically relevant tumor biomarkers. Specifically, biomarkers associated with prevalent cancers, such as breast, prostate, and lung cancers, serve as the starting point for identifying the most suitable photonic sensing platforms. The analysis underscores the need to align sensor design with the physicochemical properties of each biomarker and the operational requirements of the application. No photonic platform is universally optimal; rather, each exhibits specific strengths depending on performance metrics such as sensitivity, limit of detection, and easy system integration. Within this framework, the review provides a comprehensive assessment of emerging photonic biosensors and outlines key priorities to support their effective clinical translation in cancer diagnostics. Full article
(This article belongs to the Special Issue Lab-on-a-Chip Devices for Point-of-Care Diagnostics)
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46 pages, 1152 KiB  
Systematic Review
Key Determinants Influencing Treatment Decision-Making for and Adherence to Active Surveillance for Prostate Cancer: A Systematic Review
by Pani Nasseri, Jorien Veldwijk, Christa Niehot, Esmee F. H. Mulder, Esther W. de Bekker-Grob, Monique J. Roobol and Lionne D. F. Venderbos
J. Pers. Med. 2025, 15(7), 315; https://doi.org/10.3390/jpm15070315 - 15 Jul 2025
Viewed by 640
Abstract
Background/Objectives: Men choosing active surveillance (AS) for low- and intermediate risk prostate cancer (PCa) must weigh its harms and benefits against those of active treatment (AT). To understand factors influencing treatment decision-making (TDM) for and adherence to AS, we performed a systematic [...] Read more.
Background/Objectives: Men choosing active surveillance (AS) for low- and intermediate risk prostate cancer (PCa) must weigh its harms and benefits against those of active treatment (AT). To understand factors influencing treatment decision-making (TDM) for and adherence to AS, we performed a systematic review. Methods: This systematic review followed the PRISMA guidelines and was registered with PROSPERO (ID CRD42024490427). A comprehensive search strategy from 1990 to 2024 was executed across multiple databases, including Medline and Embase. Studies were included if they examined factors influencing TDM for AS or active monitoring (AM) and adherence to AS/AM. Results: Of the 8316 articles identified, 223 articles were eligible for inclusion. The decision for AS was influenced by different factors, including comprehensive information about treatment options, social support, and wanting to avoid side-effects. Key reasons to choose AT over AS included a lack of information from healthcare professionals about AS and fear of disease progression. Reasons for adhering to the AS protocol included better quality of life and social support. While non-adherence to the AS protocol is prompted by, e.g., biopsy burden and uncertainty, AS discontinuation is generally a results of medical reasons (namely disease upgrading) or from anxiety and family pressure. Conclusions: Numerous factors influence men’s treatment pathway choices. Involving family members in shared decision-making and ensuring that patients have detailed information about AS as a treatment option could help to improve AS uptake. Addressing psychosocial challenges through education and family involvement could improve AS adherence. These insights can help healthcare providers by addressing men’s needs during TDM and AS. Full article
(This article belongs to the Section Personalized Therapy and Drug Delivery)
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19 pages, 1773 KiB  
Systematic Review
Immunomodulatory Effects of Anesthetic Techniques in Lung Cancer Surgery: A Systematic Review and Meta-Analysis
by Georgios Konstantis, Ilias Katsadouros, Georgia Tsaousi, Vasileios Grosomanidis and Chryssa Pourzitaki
Medicina 2025, 61(7), 1263; https://doi.org/10.3390/medicina61071263 - 12 Jul 2025
Viewed by 277
Abstract
Background and Objectives: Lung cancer represents one of the principal causes of cancer-associated mortality worldwide. Despite the numerous novel therapeutic agents, surgical resection remains, in many cases, the mainstay treatment. A growing body of evidence indicates that the anesthetic technique of choice [...] Read more.
Background and Objectives: Lung cancer represents one of the principal causes of cancer-associated mortality worldwide. Despite the numerous novel therapeutic agents, surgical resection remains, in many cases, the mainstay treatment. A growing body of evidence indicates that the anesthetic technique of choice contributes to perioperative immunosuppression, thus having an impact on cancer recurrence and prognosis. The aim of this systematic review is to provide a thorough summary of the current literature regarding the modulation of the immune response induced by the various anesthetic techniques that are used in lung cancer surgery, with a particular emphasis on cellular immunity. Materials and Methods: PubMed, Scopus, and the Cochrane databases were systematically searched from November 2023 up to March 2024 to identify randomized controlled trials (RCTs) that met the eligibility criteria. Results: A total of seven RCTs were included. Four of the RCTs compared the administration of general anesthesia alone versus general anesthesia combined with epidural anesthesia. The subsequent meta-analysis showed that the combination of general and epidural anesthesia exerted a positive impact on the cell counts of the CD3+ cells (SMD −0.42, 95% Cl −0.70 to −0.13 24 h postoperatively and SMD −0.86 95% Cl −1.48 to −0.23 72 h postoperatively), the CD4+ cells (SMD −0.41 95% Cl −0.69 to −0.12 at the end of surgery and SMD −0.56 95% Cl −0.85 to −0.27 72 h later), and the CD4+/CD8+ ratio (SMD −0.31 95% Cl −0.59 to −0.02 immediately after surgery, SMD −0.50 95% Cl −0.86 to −0.14 24 h postoperatively, and SMD −0.60 95% Cl −0.89 to −0.31 72 h later). The pooled results regarding CD8+ and NK cell counts were inconclusive. The remaining three studies compared volatile-based anesthesia with total intravenous anesthesia (TIVA). Due to disparities between these studies, qualitative analysis was inconclusive, whereas quantitative analysis was not feasible. Conclusions: The supplementation of general anesthesia with epidural anesthesia favorably impacts CD3+ and CD4+ cell counts, as well as the CD4+/CD8+ ratio. The present results and the effects of anesthetic technique on other immune cells must be consolidated with further high-quality studies. Full article
(This article belongs to the Section Pharmacology)
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12 pages, 567 KiB  
Article
Toxicity Profiles of Antibody–Drug Conjugates: Synthesis and Graphical Insights to Optimize Patient-Centered Treatment Strategies for HER2-Negative Metastatic Breast Cancer
by Bérénice Collineau, Anthony Gonçalves, Marie Domon, Damien Bruyat, François Bertucci and Alexandre de Nonneville
Cancers 2025, 17(14), 2307; https://doi.org/10.3390/cancers17142307 - 11 Jul 2025
Viewed by 433
Abstract
Background: The treatment options for HER2-negative metastatic breast cancer include targeted therapies, cytotoxic chemotherapies, and immunotherapy. However, limited specificity and inevitable resistance highlight the need for novel agents. Antibody–drug conjugates (ADCs), such as trastuzumab deruxtecan (T-DXd) and sacituzumab govitecan (SG), represent a breakthrough [...] Read more.
Background: The treatment options for HER2-negative metastatic breast cancer include targeted therapies, cytotoxic chemotherapies, and immunotherapy. However, limited specificity and inevitable resistance highlight the need for novel agents. Antibody–drug conjugates (ADCs), such as trastuzumab deruxtecan (T-DXd) and sacituzumab govitecan (SG), represent a breakthrough by selectively delivering cytotoxic agents to tumor cells, potentially improving the therapeutic index. Despite demonstrated efficacy, ADCs present toxicity profiles similar to conventional chemotherapy, alongside unique adverse events. In clinical practice, oncologists may face scenarios where both T-DXd and SG are treatment options in HER2-negative mBC. To enable shared decision-making, it is crucial to present a comprehensive overview that includes both efficacy data and detailed toxicity profiles. Our objective was to provide a pooled and informative synthesis of toxicities from pivotal studies, including graphical representations, to support informed, patient-centered medical decisions. Methods: We reviewed safety data from phase 3 clinical trials in HER2-negative mBC: DESTINY-Breast04/DESTINY-Breast06 for T-DXd and ASCENT/TROPICS-02 for SG. Adverse event (AE) profiles, including frequency and severity, were extracted, and weighted means were calculated. Emerging ADCs such as datopotamab deruxtecan and patritumab deruxtecan were considered to contextualize future therapeutic decisions. Results: Tables, bar plots and radar plots were generated. T-DXd demonstrated high rates of nausea (69.2%), fatigue (47.2%), and neutropenia (35.6%), with 52.7% experiencing grade ≥ 3 AEs. Notably, pneumonitis occurred in 10.7%, with grade ≥ 3 in 2.6%. SG showed a distinct AE profile, with higher incidences of neutropenia (67.1%), with grade ≥ 3 in 51.3%, and diarrhea (60.8%). Conclusions: The choice between ADCs in HER2-negative metastatic BC when both T-DXd and SG are treatment options should consider toxicity profiles to optimize patient-centered treatment strategies. Tailoring ADC selection based on individual tolerance and preferences is critical for shared decision-making, and future research should focus on assessing the utility and acceptability of such clinical tools to guide treatment selection. Full article
(This article belongs to the Section Cancer Drug Development)
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10 pages, 778 KiB  
Case Report
A Rare Case of Exophiala Dermatitidis Isolation in a Patient with Non-Cystic Fibrosis Bronchiectasis: Colonization or True Infection?
by Francesco Rocco Bertuccio, Nicola Baio, Simone Montini, Valentina Ferroni, Vittorio Chino, Lucrezia Pisanu, Marianna Russo, Ilaria Giana, Elisabetta Gallo, Lorenzo Arlando, Klodjana Mucaj, Mitela Tafa, Maria Arminio, Emanuela De Stefano, Alessandro Cascina, Angelo Guido Corsico, Giulia Maria Stella and Valentina Conio
Diagnostics 2025, 15(13), 1661; https://doi.org/10.3390/diagnostics15131661 - 29 Jun 2025
Viewed by 493
Abstract
Background: Exophiala dermatitidis is a dematiaceous, thermotolerant, yeast-like fungus increasingly recognized as an opportunistic pathogen in chronic airway diseases. While commonly associated with cystic fibrosis, its clinical significance in non-cystic fibrosis bronchiectasis (NCFB) remains unclear. Case Presentation: We report the case of [...] Read more.
Background: Exophiala dermatitidis is a dematiaceous, thermotolerant, yeast-like fungus increasingly recognized as an opportunistic pathogen in chronic airway diseases. While commonly associated with cystic fibrosis, its clinical significance in non-cystic fibrosis bronchiectasis (NCFB) remains unclear. Case Presentation: We report the case of a 66-year-old immunocompetent woman with a history of breast cancer in remission and NCFB, who presented with chronic cough and dyspnea. Chest CT revealed bilateral bronchiectasis with new pseudonodular opacities. Bronchoalveolar lavage cultures identified E. dermatitidis, along with Pseudomonas aeruginosa and methicillin-sensitive Staphylococcus aureus. Given clinical stability and the absence of systemic signs, initial therapy included oral voriconazole, levofloxacin, doxycycline, and inhaled amikacin. Despite persistent fungal isolation on repeat bronchoscopy, the patient remained asymptomatic with stable radiologic and functional findings. Antifungal therapy was discontinued, and the patient continued under close monitoring. The patient exhibited clinical and radiological stability despite repeated fungal isolation, reinforcing the hypothesis of persistent colonization rather than active infection. Discussion: This case underscores the diagnostic challenges in distinguishing fungal colonization from true infection in structurally abnormal lungs. In NCFB, disrupted mucociliary clearance and microbial dysbiosis may facilitate fungal persistence, even in the absence of overt immunosuppression. The detection of E. dermatitidis should prompt a comprehensive evaluation, integrating clinical, radiologic, and microbiologic data to guide management. Voriconazole is currently the antifungal agent of choice, though therapeutic thresholds and duration remain undefined. Conclusions: This report highlights the potential role of E. dermatitidis as an under-recognized respiratory pathogen in NCFB and the importance of a multidisciplinary, individualized approach to diagnosis and treatment. This case underscores the need for further research on fungal colonization in NCFB and the development of evidence-based treatment guidelines. Further studies are needed to clarify the pathogenic significance, optimal management, and long-term outcomes of E. dermatitidis in non-CF chronic lung diseases. Full article
(This article belongs to the Section Diagnostic Microbiology and Infectious Disease)
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25 pages, 751 KiB  
Review
Perioperative Management of Non-Small Cell Lung Cancer in the Era of Immunotherapy
by Ulas Kumbasar, Erkan Dikmen, Zeliha Gunnur Dikmen, Ates Tenekeci, Ilgen Mender, Sergei Gryaznov, Burak Bilgin and Saadettin Kilickap
Cells 2025, 14(13), 971; https://doi.org/10.3390/cells14130971 - 25 Jun 2025
Viewed by 831
Abstract
Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality worldwide. Nonetheless, deeper molecular understanding of NSCLC has resulted in novel therapeutic approaches, including targeted therapy and immunotherapy, which have improved patient prognosis and outcomes in recent years. Immune checkpoint inhibitors [...] Read more.
Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality worldwide. Nonetheless, deeper molecular understanding of NSCLC has resulted in novel therapeutic approaches, including targeted therapy and immunotherapy, which have improved patient prognosis and outcomes in recent years. Immune checkpoint inhibitors (ICIs), with or without chemotherapy, are now considered valuable components of treatment for NSCLC cases that do not have specific actionable genetic mutations. Patients with actionable genetic mutations are candidates for targeted therapies. The primary focus of this review is the rationale for using ICIs in the perioperative setting for patients with resectable NSCLC and in advanced disease settings. Furthermore, we compare the benefits of using ICIs with the challenges associated with their clinical implementation in resectable and advanced NSCLC. Finally, we emphasize the development of novel treatment strategies that potentially provide an optimal treatment choice for patients with advanced NSCLC. Full article
(This article belongs to the Special Issue Cellular Mechanisms of Anti-Cancer Therapies)
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20 pages, 3005 KiB  
Article
Phenotypic Plasticity and Androgen Receptor Bypass Drive Cross-Resistance to Apalutamide in Castration-Resistant Prostate Cancer Cell Models
by Iris Simon, Jose Manuel Sanchez-Manas, Sonia Perales, Gonzalo Martinez-Navajas, Jorge Ceron-Hernandez and Pedro J. Real
Int. J. Mol. Sci. 2025, 26(13), 5939; https://doi.org/10.3390/ijms26135939 - 20 Jun 2025
Viewed by 540
Abstract
The treatment of choice for prostate cancer is androgen deprivation (ADT) and novel hormonal agents such as Abiraterone, Enzalutamide, or Apalutamide. Initially, this therapy is highly effective, but a significant challenge arises as most patients eventually develop resistance, resulting in castration-resistant prostate cancer [...] Read more.
The treatment of choice for prostate cancer is androgen deprivation (ADT) and novel hormonal agents such as Abiraterone, Enzalutamide, or Apalutamide. Initially, this therapy is highly effective, but a significant challenge arises as most patients eventually develop resistance, resulting in castration-resistant prostate cancer (CRPC). Furthermore, the sequential use of these drugs can lead to cross-resistance, diminishing their efficacy. Tumor heterogeneity plays a pivotal role in the development of resistance to different treatments. This study utilized cellular models of CRPC to assess the response to Apalutamide when it was administered as a second- or third-line treatment. Functional and genetic analyses were conducted in various CRPC cell models exposed to Apalutamide. These analyses included real-time cell monitoring assays, flow cytometry, clonogenicity assays, and RT-qPCR. CRPC cell models were capable of continued proliferation, maintained cell cycle profiles similar to those of untreated cells, and retained their clonogenic potential. Cross-resistance to Apalutamide in models of ADT, ADT plus Enzalutamide, or Abiraterone resistance did not correlate with the expression levels of AR-V7 and AR-V9 variants. Gene expression analysis of resistant prostate cancer cell lines revealed that treatment with Apalutamide induced the emergence of more aggressive phenotypes, including cancer stem cells or neuroendocrine differentiation profiles. Most CRPC cell models developed cross-resistance to Apalutamide and were able to proliferate and retain their clonogenic capability. Apalutamide resistance was not linked to the expression of AR-V7 or AR-V9 variants but was instead associated to bypass of AR signaling pathway and the emergence of more aggressive expression profiles. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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12 pages, 2458 KiB  
Systematic Review
Recurrence Pattern of Left Upper Lobectomies and Trisegmentectomies: Systematic Review and Meta-Analysis
by Borja Aguinagalde, Juan A. Ferrer-Bonsoms, Iker López, Jon Ander Lizarbe, Arantza Fernandez-Monge, Maria Mainer, Raul Embun and Jon Zabaleta
J. Clin. Med. 2025, 14(12), 4385; https://doi.org/10.3390/jcm14124385 - 19 Jun 2025
Viewed by 415
Abstract
Background: Surgical resection remains the standard treatment for early-stage non-small-cell lung cancer (NSCLC). Traditionally, lobectomy has been considered the procedure of choice; however, emerging evidence suggests that trisegmentectomy may offer comparable outcomes. This meta-analysis evaluates whether left upper lobe trisegmentectomy provides non-inferior or [...] Read more.
Background: Surgical resection remains the standard treatment for early-stage non-small-cell lung cancer (NSCLC). Traditionally, lobectomy has been considered the procedure of choice; however, emerging evidence suggests that trisegmentectomy may offer comparable outcomes. This meta-analysis evaluates whether left upper lobe trisegmentectomy provides non-inferior or superior oncologic outcomes compared to left upper lobectomy, with particular attention to recurrence patterns. Methods: Following PRISMA guidelines, we included comparative studies evaluating left upper lobectomy versus trisegmentectomy. Outcomes assessed included recurrence (locoregional and distant), morbidity, and the length of hospital stay. A meta-analysis was conducted using the metabin function from the R meta package. Results: Of 14 identified articles, 9 met the inclusion criteria. No significant differences were observed in locoregional recurrence. However, distant recurrence was significantly lower in the trisegmentectomy group (OR 0.58; 95% CI 0.41–0.82). While overall morbidity showed no significant difference (OR 0.95), analysis of matched studies favored trisegmentectomy (OR 0.73; 95% CI 0.56–0.96). Hospital stay was significantly shorter in the trisegmentectomy group (OR –0.94; 95% CI –1.26 to –0.63). Conclusions: Trisegmentectomy and lobectomy exhibit distinct recurrence patterns, with lobectomy associated with a higher rate of distant recurrence. Trisegmentectomy may provide oncologic and perioperative advantages in appropriately selected patients. The systematic review and meta-analysis are registered in PROSPERO (registration number: CRD420251066445). Full article
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8 pages, 677 KiB  
Article
Transperineal Prostate Biopsy Under Local Anaesthesia, Tolerability, and Functional Outcomes: A Prospective, Monocentric, and Single-Operator Study
by Gilles Adans-Dester, Mathieu Bourguignon and Guillaume Krings
J. Clin. Med. 2025, 14(12), 4377; https://doi.org/10.3390/jcm14124377 - 19 Jun 2025
Viewed by 580
Abstract
Background: Prostate cancer (PCa) remains a major health concern worldwide, although improved screening and treatments have reduced its incidence and mortality. MRI-targeted biopsies, especially using MRI–ultrasound fusion, enhance detection of clinically significant prostate cancer (CsPCa) and reduce unnecessary procedures. Transperineal biopsies offer [...] Read more.
Background: Prostate cancer (PCa) remains a major health concern worldwide, although improved screening and treatments have reduced its incidence and mortality. MRI-targeted biopsies, especially using MRI–ultrasound fusion, enhance detection of clinically significant prostate cancer (CsPCa) and reduce unnecessary procedures. Transperineal biopsies offer the same diagnostic performance and reduce the risk of infection while limiting the need for antibiotic prophylaxis. However, they tend to be more painful under local anaesthesia and require greater operator experience. Methods: This study prospectively assessed the tolerability and effectiveness of transperineal targeted biopsies under local anaesthesia in a monocentric cohort of 51 patients. Results: Immediate pre-biopsy anxiety showed a clinically significant association with pain experienced during biopsies, and greater expected pain resulted in greater experienced pain. Overall patient tolerability was high. Local anaesthesia provided procedural flexibility, reduced resource utilisation, was cost-effective, and did not compromise precision. Conclusions: The results support local anaesthesia as a viable option, offering precision, patient satisfaction, and reduced healthcare resource utilisation. These results emphasise the importance of personalising the choice of anaesthesia modality for transperineal prostate biopsies, tailoring it to the patient’s anxiety. Larger studies are required to confirm these findings and validate the observed trends. Full article
(This article belongs to the Section Oncology)
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18 pages, 847 KiB  
Article
Predictive Factors Aiding in the Estimation of Intraoperative Resources in Gastric Cancer Oncologic Surgery
by Alexandru Blidișel, Mihai-Cătălin Roșu, Andreea-Adriana Neamțu, Bogdan Dan Totolici, Răzvan-Ovidiu Pop-Moldovan, Andrei Ardelean, Valentin-Cristian Iovin, Ionuț Flaviu Faur, Cristina Adriana Dehelean, Sorin Adalbert Dema and Carmen Neamțu
Cancers 2025, 17(12), 2038; https://doi.org/10.3390/cancers17122038 - 18 Jun 2025
Viewed by 355
Abstract
Background/Objectives: Operating rooms represent valuable and pivotal units of any hospital. Therefore, their management affects healthcare service delivery through rescheduling, staff shortage/overtime, cost inefficiency, and patient dissatisfaction, among others. To optimize scheduling, we aim to assess preoperative evaluation criteria that influence the prediction [...] Read more.
Background/Objectives: Operating rooms represent valuable and pivotal units of any hospital. Therefore, their management affects healthcare service delivery through rescheduling, staff shortage/overtime, cost inefficiency, and patient dissatisfaction, among others. To optimize scheduling, we aim to assess preoperative evaluation criteria that influence the prediction of surgery duration for gastric cancer (GC) patients. In GC, radical surgery with curative intent is the ideal treatment. Nevertheless, the intervention sometimes must be palliative if the patient’s status and tumor staging prove too advanced. Methods: A 6-year retrospective cohort study was performed in a tertiary care hospital, including all cases diagnosed with GC (ICD-10 code C16), confirmed through histopathology, and undergoing surgical treatment (N = 108). Results: The results of our study confirm male predominance (63.89%) among GC surgery candidates while bringing new perspectives on patient evaluation criteria and choice of surgical intervention (curative—Group 1, palliative—Group 2). Surgery duration, including anesthesiology (175.19 [95% CI (157.60–192.77)] min), shows a direct correlation with the number of lymph nodes dissected (Surgical duration [min] = 10.67 × No. of lymph nodes removed − 32.25). Interestingly, the aggressiveness of the tumor based on histological grade (highly differentiated being generally less aggressive than poorly differentiated) shows differential correlation with surgery duration among curative and palliative surgery candidates. Similarly, TNM staging indicates the need for a longer surgical duration (pTNM stage IIA, IIB, and IIIA) for curative interventions in patients with less advanced stages, as opposed to shorter surgery duration for palliative interventions (pTNM stage IIIC and IV). Conclusions: The study quantitatively presents the resources needed for the optimal surgical treatment of different groups of GC patients, as the disease coding systems in use regard the treatment of each pathology as “standard” in terms of patient management. The results obtained are anchored in the global perspectives of surgical outcomes and aim to improve the management of operating room scheduling, staff, and resources. Full article
(This article belongs to the Special Issue State-of-the-Art Research on Gastric Cancer Surgery)
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14 pages, 603 KiB  
Review
SIU-ICUD: Focal Therapy for PCa — The Technique
by Lara Rodriguez-Sanchez, Thomas J. Polascik, Kara Watts, Peter Ka-Fung Chiu, Mark Emberton, Behfar Ehdaie, Hashim U. Ahmed, Andre Abreu, Ardeshir R. Rastinehad and Rafael Sanchez-Salas
Soc. Int. Urol. J. 2025, 6(3), 38; https://doi.org/10.3390/siuj6030038 - 7 Jun 2025
Cited by 1 | Viewed by 1047
Abstract
Background/Objectives: Focal therapy (FT) and technology are closely connected. Advanced imaging allows for precise identification of the index lesion, enabling the targeted use of various thermal and non-thermal energy sources through different approaches, with specific techniques tailored to lesion location and operator expertise. [...] Read more.
Background/Objectives: Focal therapy (FT) and technology are closely connected. Advanced imaging allows for precise identification of the index lesion, enabling the targeted use of various thermal and non-thermal energy sources through different approaches, with specific techniques tailored to lesion location and operator expertise. This personalized approach enhances both safety and effectiveness, facilitating customized treatment planning. Methods: The International Consultation on Urological Diseases formed a committee to review the current literature on FT for prostate cancer (PCa), focusing specifically on the technique. Following in-depth discussions, the committee chose a “by lesion” approach rather than the traditional “by energy” approach to structure the review. A comprehensive PubMed search was conducted to gather relevant articles on the various energy modalities and procedural approaches used in FT for PCa. Results: Lesions in the apex, anterior, and posterior regions of the prostate can be accessed through several FT approaches, each associated with specific energy modalities and techniques. The transrectal approach utilizes high-intensity focused ultrasound (HIFU) and focal laser ablation (FLA), while the transperineal approach is compatible with energy sources such as cryotherapy, irreversible electroporation (IRE), brachytherapy, and FLA. The transurethral approach supports methods such as transurethral ultrasound ablation (TULSA). Each approach offers distinct advantages based on lesion location, treatment area, and energy modality. The choice of technique evaluated the safety and efficacy of each energy source and approach based on specific treatment areas within the prostate, highlighting the need for robust research across lesion locations and modalities, rather than focusing solely on each modality for a specific region. Conclusions: FT is rapidly advancing with new energy sources, technological improvements, and increasing operator expertise. To further optimize FT, research should prioritize evaluating the safety and effectiveness of different energy sources for various lesion locations, focusing on the treatment area rather than the energy modality itself. Full article
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