Search Results (1,344)

Prostate cancer (PCa) is the second most frequently diagnosed malignancy in men worldwide. Although traditionally considered a disease of older men, the incidence of early-onset PCa (diagnosis < 55 years) is steadily rising. Advances in screening and therapy have significantly improved survival, creating a growing cohort of younger survivors for whom post-treatment quality of life—notably reproductive function—is paramount. Curative treatments such as radical prostatectomy, pelvic radiotherapy, androgen-deprivation therapy (ADT), and chemotherapy often cause irreversible infertility via multiple mechanisms, including surgical disruption of the ejaculatory tract, endocrine suppression of spermatogenesis, direct gonadotoxic injury to the testes, and oxidative sperm DNA damage. Despite these risks, fertility preservation is frequently overlooked in pre-treatment counseling, leaving many patients unaware of their options. This narrative review synthesizes current evidence on how PCa therapies impact male fertility, elucidates the molecular and physiological mechanisms of iatrogenic infertility, and evaluates both established and emerging strategies for fertility preservation and restoration. Key interventions covered include sperm cryopreservation, microsurgical testicular sperm extraction (TESE), and assisted reproductive technologies (ART). Psychosocial factors influencing decision-making, novel biomarkers predictive of post-treatment spermatogenic recovery, and long-term offspring outcomes are also examined. The review underscores the urgent need for timely, multidisciplinary fertility consultation as a routine component of PCa care. As PCa increasingly affects men in their reproductive years, proactively integrating preservation into standard oncologic practice should become a standard survivorship priority. Full article

Background/Objectives: Pancreatic cancer (PC) is the seventh leading cause of cancer-related deaths worldwide, with its incidence rising each year. Despite its relatively low incidence, the aggressiveness of pancreatic cancer results in high mortality, with only 12% of patients surviving five years post-diagnosis. Surgical resection remains the only potentially curative treatment, but the tumor is often diagnosed at an advanced stage. The goal of this work is to identify vulnerabilities that can affect the efficacy of treatments and improve the efficacy of therapy. Methods: MAP17 overexpression in pancreatic cancer cell lines, RT-qPCR analysis, xenografts, in vitro and in vivo treatments, analysis of data from pancreatic tumors in transcriptomic patient databases. Results: We studied the prognostic and predictive value of MAP17 (PDZK1IP1) expression in pancreatic cancer, and we found that high MAP17 mRNA expression was associated with poor prognosis. In addition, single-cell analysis revealed that high MAP17 expression was present only in tumor cells. We investigated whether the response to various antitumor agents depended on MAP17 expression. In 2D culture, MAP17-expressing pancreatic cancer cells responded better to gemcitabine and 5-fluorouracil. However, in vivo xenograft tumors with MAP17 expression showed resistance to all treatments. Additionally, MAP17-expressing cells had a high NAD pool, which seems to be effectively depleted in vivo by NAMPT inhibitors, the primary enzyme for NAD biosynthesis. Conclusions: Our findings suggest that MAP17 expression could enhance the prognostic stratification of pancreatic cancer patients. Moreover, the coadministration of NAMPT inhibitors with current treatments may sensitize tumors with high MAP17 expression to chemotherapy and improve the efficacy of chemotherapy. Full article

Background/Objectives: As novel synergistic strategy for heart failure (HF), this study explores the formulation and characterization of liposomal systems co-loaded with SGLT2 inhibitors (dapagliflozin—DAPA and empagliflozin—EMPA) and curcumin (Cur). Methods: To enhance liposomal membrane stability and achieve sustained, controlled drug release, oleanolic acid (OA) was incorporated into the lipid bilayer, while the liposomal surface was coated with polyvinylpyrrolidone (PVP). Results: The resulting liposomes exhibited favorable physico-chemical properties (particle size ~170 nm, low PDI, negative zeta potential), high encapsulation efficiencies (up to 97%), and spherical morphology as confirmed by STEM. XRD and DSC analyses indicated successful API incorporation and amorphization within the lipid matrix, while PVP coating provided slight improvements in thermal stability. Trehalose proved to be an effective cryoprotectant, preserving liposome integrity after freeze-drying. In vitro release studies demonstrated sustained and delayed drug release, especially in PVP-coated and OA-containing formulations. Conclusions: All these findings highlight the promise of PVP-coated, OA-stabilized liposomal formulations co-loaded with SGLT2 inhibitors and Cur as biocompatible, multifunctional platforms for targeted HF therapy. Full article

Background/Objectives: Primary malignant lung tumors in children are rare and diagnostically challenging. This study presents a single-center experience in the diagnosis and treatment of these tumors, emphasizing the role of histopathological and genetic profiling in informing individualized therapeutic strategies. Methods: We retrospectively reviewed records of seven pediatric patients (ages 2–18) treated from 2015 to 2025. Diagnostics included laboratory tests, chest CT, bronchoscopy, and histopathological/immunohistochemical analysis. Treatment primarily involved surgical resection, complemented by chemo-, radio-, or targeted therapies when indicated. Results: Inflammatory myofibroblastic tumor (IMT) represented the most commonly diagnosed entity (3/7 cases). The tumors presented with nonspecific symptoms, most frequently dry cough. Tumor type distribution was age-dependent, with aggressive forms such as pleuropulmonary blastoma predominantly affecting younger children, whereas IMT and carcinoid tumors were more common in older patients. Surgical resection remained the mainstay of treatment in the majority of cases. Bronchoscopy served as a valuable adjunct in the initial management of tumors exhibiting intraluminal growth, allowing for direct visualization, tissue sampling, and partial debulking to alleviate airway obstruction. In patients with an initially unresectable IMT harboring specific gene fusion rearrangement (e.g., TFG::ROS1), neoadjuvant targeted therapy with crizotinib enabled adequate tumor shrinkage to allow for subsequent surgical resection. Two patients in the study cohort died as a result of disease progression. Conclusions: A multidisciplinary diagnostic approach—integrating radiologic, bronchoscopic, histopathological, and genetic evaluations—ensures high diagnostic accuracy. While conventional treatments remain curative in many cases, targeted therapies directed at specific molecular alterations may offer essential therapeutic options for selected patients. Full article

Most patients with non-small-cell lung cancer (NSCLC) present with advanced/metastatic disease at diagnosis, and molecular profiling is critical in guiding treatment decisions. This retrospective cohort study aimed to characterize EGFR mutations (EGFRm) in advanced/metastatic NSCLC patients, treatment patterns, and real-world outcomes. Adults diagnosed between 2018 and 2021 and treated at a Comprehensive Care Center were included. Time-to-event outcomes were analyzed using the Kaplan–Meier method. A total of 110 patients were included, with a median age of 69.0 years (range, 37–93), 76.4% female, and 83.2% non-smokers. About 97.3% had adenocarcinomas, with 93.6% at stage IV, 40.9% with ≥ three metastatic sites (brain metastases in 24.5%), 33.6% ECOG 2–4, and 58.2% with an EGFR exon-19 deletion. A minority started supportive care or curative-intent treatment, and 81.8% underwent first-line palliative systemic therapy (TKIs, 91.1%; chemotherapy, 8.9%). Median real-world overall survival (rwOS) was 18.9 months (95% CI, 13.8–28.1). Worse rwOS was observed in patients with ECOG 2–4 versus ECOG 0–1 (10.3 vs. 22.8 months; HR 1.82, 95% CI 1.17–2.85; p = 0.008) and in patients with exon-21 L858R versus exon 19 deletions (15.8 vs. 24.2 months; HR 1.59, 95% CI 1.00–2.54; p = 0.048). In patients treated with palliative systemic treatment, median progression-free survival was 10.9 months (95% CI, 8.8–13.6). This study provides important insights regarding real-world characteristics, treatment patterns, and outcomes from a cohort of EGFRm advanced/metastatic NSCLC patients. Full article

Background: Paediatric hepatocellular carcinoma (HCC), including its fibrolamellar variant (FLC), is a rare malignancy with distinct biological behaviour and limited therapeutic options. While complete surgical resection is a key determinant of survival, many patients present with unresectable tumours at diagnosis. The role of neoadjuvant chemotherapy in improving resectability, particularly in histologically distinct subtypes, remains inconclusive. Methods: We retrospectively analysed 43 patients (<18 years) with histologically confirmed conventional HCC (cHCC, n = 27) or FLC (n = 16) enrolled in the German Pediatric Liver Tumour Registry. We assessed clinical characteristics, treatment response, surgical outcomes, and survival. Special focus was placed on the impact of neoadjuvant chemotherapy in initially unresectable tumours. Results: FLC and cHCC exhibited significant differences in clinical presentation, such as age of presentation, AFP elevation, or presence of underlying liver disease. Although overall survival did not significantly differ between groups, cHCC tumours showed a markedly higher response to chemotherapy (62.5% partial remission vs. 0% in FLC). Complete resection (R0) was achieved in 77% of all patients and was the strongest predictor of survival. Importantly, a subset of cHCC patients who initially had unresectable tumours became eligible for curative surgery following neoadjuvant chemotherapy. Notably, delayed resection after chemotherapy led to outcomes comparable to those with upfront surgery, whereas progression during chemotherapy was associated with a universally poor prognosis. Conclusions: This study supports upfront resection as the preferred strategy in paediatric HCC and FLC whenever feasible. In cHCC, neoadjuvant chemotherapy demonstrated a favourable response profile and contributed to secondary resectability in a subset of initially unresectable cases, supporting a potential role within a multimodal treatment approach. In contrast, FLC showed limited responsiveness to current systemic therapies. These findings emphasise the importance of histology-specific strategies and highlight the ongoing need for more effective systemic options, particularly for unresectable FLC. Full article

Background: Circadian rhythms regulate critical cellular processes, including DNA repair and cell cycle dynamics, potentially influencing the effectiveness of radiotherapy (RT). This study evaluated whether RT timing impacts clinical outcomes and symptom burden in prostate cancer patients. Patients/Methods: This retrospective study (n = 336, median follow-up 55 months) included men who received curative intent external beam RT between 2010 and 2019 (median age 69, 69% black, median PSA 11.3, 40% with Gleason 8–10). Treatment times (TTs) were averaged and analyzed by quartile/median. Outcomes included freedom from biochemical failure (FFBF) and distant metastasis (FFDM), GI and GU toxicity, and quality of life (QOL). Subgroup analyses by race and hormone therapy status were performed. Results: Across the overall cohort, TT was not associated with FFBF or FFDM. However, in white men, earlier TTs were significantly associated with higher 5-year FFBF (89% vs. 67%, p = 0.0139) and FFDM (93% vs. 72%, p = 0.0268). In the multivariate analysis (MVA), TT was not associated with FFBF or FFDM for all men, but in white men, earlier TT was associated with improved FFBF (HR 2.8, p = 0.06) in a model also including risk category (p = 0.21). Overall, no significant differences were observed for grade 2–3+ toxicity and TT. Trends for inferior QOL, and worse grade 2+ (p = 0.2) and 3+ GU toxicity (p = 0.1) were observed for later TTs. In white men, bowel, urinary continence, and irritative/obstructive urinary QOL were worse with later TTs (p < 0.05). Conclusions: TT may influence clinical outcomes and symptom burden, particularly in white men. These findings underscore the potential of chronoradiotherapy as a personalized treatment strategy and highlight the need for prospective trials. Full article

Polycystic liver disease (PLD) is a rare genetic disorder characterized by the development of >10 fluid-filled cysts in the liver. While PLD can occur in isolation, it is most commonly associated with autosomal dominant polycystic kidney disease, adding complexity to its management. PLD is often asymptomatic but can lead to hepatomegaly, causing symptoms such as abdominal distension, pain and discomfort, early satiety, gastroesophageal reflux, and malnutrition, ultimately affecting patients’ quality of life. Current treatment strategies, including pharmacological and interventional approaches, focus on reducing liver volume and alleviating symptoms. However, management remains largely symptomatic, as no definitive therapies exist to halt cyst progression. Liver transplantation is the only curative option for patients with severe, progressive disease and refractory complications. The EASL guidelines recognize that PLD-related symptoms, primarily due to hepatomegaly, can contribute to involuntary weight loss and recommend assessing symptomatic patients for malnutrition and sarcopenia. Although evidence suggests that patients with PLD may be at risk of malnutrition, original data on the quality and extent of nutritional alterations remain scarce. The potential influence of nutrition on disease progression, symptom burden, and overall well-being is also largely unexplored. Given these knowledge gaps, addressing nutritional challenges, such as early satiety, is essential for optimizing symptom management and maintaining overall nutritional status. This review outlines a possible pathophysiology of malnutrition, specific dietary considerations and recommendations, and weight management in patients with PLD. Additionally, dietary complexities in patients with concurrent renal involvement are discussed, offering a practical framework for clinicians and dietitians in managing this challenging condition. Full article

Objectives: Colorectal cancer (CRC) is a leading cause of cancer-related mortality, driven by chronic inflammation, gut microbiota dysbiosis, and complex tumor microenvironment interactions. Current therapies are limited by systemic toxicity and poor tumor accumulation. This study aimed to develop a ROS/enzyme dual-responsive oral drug delivery system, KGM-CUR/PSM microspheres, to achieve precise drug release in CRC and enhance tumor-specific drug accumulation, which leverages high ROS levels in CRC and the β-mannanase overexpression in colorectal tissues. Methods: In this study, we synthesized a ROS-responsive prodrug polymer (PSM) by conjugating polyethylene glycol monomethyl ether (mPEG) and mesalazine (MSL) via a thioether bond. CUR was then encapsulated into PSM using thin-film hydration to form tumor microenvironment-responsive micelles (CUR/PSM). Subsequently, konjac glucomannan (KGM) was employed to fabricate KGM-CUR/PSM microspheres, enabling targeted delivery for colorectal cancer therapy. The ROS/enzyme dual-response properties were confirmed through in vitro drug release studies. Cytotoxicity, cellular uptake, and cell migration were assessed in SW480 cells. In vivo efficacy was evaluated in AOM/DSS-induced CRC mice, monitoring tumor growth, inflammatory markers (TNF-α, IL-1β, IL-6, MPO), and gut microbiota composition. Results: In vitro drug release studies demonstrated that KGM-CUR/PSM microspheres exhibited ROS/enzyme-responsive release profiles. CUR/PSM micelles demonstrated significant anti-CRC efficacy in cytotoxicity assays, cellular uptake studies, and cell migration assays. In AOM/DSS-induced CRC mice, KGM-CUR/PSM microspheres significantly improved survival and inhibited CRC tumor growth, and effectively reduced the expression of inflammatory cytokines (TNF-α, IL-1β, IL-6) and myeloperoxidase (MPO). Histopathological and microbiological analyses revealed near-normal colon architecture and microbial diversity in the KGM-CUR/PSM group, confirming the system’s ability to disrupt the “inflammation-microbiota-tumor” axis. Conclusions: The KGM-CUR/PSM microspheres demonstrated a synergistic enhancement of anti-tumor efficacy by inducing apoptosis, alleviating inflammation, and modulating the intestinal microbiota, which offers a promising stimuli-responsive drug delivery system for future clinical treatment of CRC. Full article

Gene therapy has emerged as a promising treatment for several eye diseases since it may restore vision and stop blindness. Many eye diseases, including retinitis pigmentosa and macular degeneration, have historically been rather difficult to treat and usually cause permanent vision loss. However, thanks to advances in gene therapy, many disorders can now be effectively targeted and genetically changed, providing a safer, more direct, maybe even curative approach. By introducing, altering, or repairing specific genes inside the eye, gene therapy seeks to fix the defective genes causing these disorders, thereby improving general eye health and visual ability. Voretigene neparvovec is one FDA- and EMA-approved treatment for RPE65 mutations. Retinitis pigmentosa, age-related macular degeneration, X-linked retinoschisis, choroideremia, and Stargardt disease are among the several eye disorders still under clinical trials, and experimental treatment is in progress. As research on gene therapy develops, it opens the path for groundbreaking treatments that could fundamentally change the ophthalmic care scene. Full article

Background: Gastric signet-ring cell carcinoma (GSRCC) is an aggressive gastric cancer subtype with limited evidence supporting the role of neoadjuvant chemotherapy (NAC). This study evaluated the impact of NAC on overall survival (OS) in a large, population-based cohort. Methods: We analyzed data from the SEER database (2011–2018), identifying patients aged 20–80 years with primary gastric tumors (C16.0–C16.9) and signet-ring cell histology who underwent curative-intent gastrectomy. Patients with metastatic disease, non-curative surgery, clinical Stage I, incomplete staging, or unknown survival were excluded. OS was assessed using Kaplan–Meier analysis and multivariable Cox regression. Subgroup analyses evaluated the interaction of NAC with tumor location and clinical stage. Results: A total of 978 patients met inclusion criteria; 436 (44.6%) received NAC. The 3- and 5-year OS rates were 43.9% and 38.3%, respectively. NAC was not associated with improved OS compared to surgery alone (5-year OS: 39.7% vs. 37.2%; log-rank p = 0.34) and was not an independent prognostic factor in multivariable analysis (p = 0.651). Independent predictors of worse OS included larger tumor size, advanced stage, positive nodal status, and Black race (all p < 0.05). Subgroup analysis indicated a survival benefit from NAC in patients with mid or distal gastric tumors (p < 0.001 for interaction). Conclusions: In this SEER-based analysis, NAC did not improve OS in the overall GSRCC population. However, selected subgroups may derive benefit, supporting a personalized approach to neoadjuvant therapy in GSRCC. Full article

The advent of immune checkpoint inhibitors (ICIs) has revolutionized cancer treatment, significantly improving patient outcomes across multiple malignancies. Nonetheless, these therapies are associated with immune-related adverse effects, including cardiotoxicity, which remains a critical concern. This review provides a comprehensive analysis of ICI-related cardiotoxicity, encompassing its pathophysiological mechanisms, risk factors, diagnostic modalities, and management strategies. The onset of cardiotoxicity varies widely, ranging from acute myocarditis to long-term cardiovascular complications. Early identification through clinical assessment, biomarkers, and advanced imaging techniques is crucial for timely intervention. Management strategies include high-dose corticosteroids, other immunosuppressive agents, and supportive therapies, with a focus on balancing oncologic efficacy and cardiovascular safety. Additionally, rechallenging patients with ICIs following cardiotoxic events remains a complex clinical decision requiring multidisciplinary evaluation. As immunotherapy indications expand to include high-risk populations in a curative setting too, optimizing screening, prevention, and treatment strategies is essential to mitigate cardiovascular risks. A deep understanding of the molecular and clinical aspects of ICI-related cardiotoxicity will enhance patient safety and therapeutic decision-making, underscoring the need for ongoing research in this rapidly evolving field. Full article

Pancreatic cancer is an aggressive malignancy, with a current 5-year survival rate in the United States of approximately 13.3%. Although the current standard for resectable pancreatic cancer most commonly includes neoadjuvant chemotherapy prior to a curative resection, surgery, in the majority of patients, has historically been palliative. The latter interventions include open or laparoscopic bypass of the bile duct or stomach in cases of obstructive jaundice or gastric outlet obstruction, respectively. Non-surgical interventional therapies started with percutaneous transhepatic biliary drainage (PTBD), both as a palliative maneuver in unresectable patients with obstructive jaundice and to improve liver function in patients whose surgery was delayed. Likewise, interventional radiologic techniques included the placement of plastic and ultimately self-expandable metal stents (SEMSs) through PTBD tracts in patients with unresectable cancer as well as percutaneous cholecystostomy in patients who developed cholecystitis in the context of malignant obstructive jaundice. Endoscopic retrograde cholangiopancreatography (ERCP) and stent placement (plastic/SEMS) were subsequently used both preoperatively and palliatively, and this was followed by, or undertaken in conjunction with, endoscopic gastro-duodenal SEMS placement for gastric outlet obstruction. Although endoscopic ultrasound (EUS) was initially used to cytologically diagnose and stage pancreatic cancer, early palliation included celiac block or ablation for intractable pain. However, it took the development of lumen-apposing metal stents (LAMSs) to facilitate a myriad of palliative procedures: cholecystoduodenal, choledochoduodenal, gastrohepatic, and gastroenteric anastomoses for cholecystitis, obstructive jaundice, and gastric outlet obstruction, respectively. In this review, we outline these procedures, which have variably supplanted surgery for the palliation of pancreatic cancer in this rapidly evolving field. Full article

Duchenne muscular dystrophy (DMD) is a severe X-linked disorder characterized by progressive muscle degeneration due to mutations in the dystrophin gene. Despite major advancements in understanding its pathophysiology, there is still no curative treatment. This review provides an up-to-date overview of current and emerging therapeutic approaches—including antisense oligonucleotides, gene therapy, gene editing, corticosteroids, and histone deacetylases(HDAC) inhibitors—aimed at restoring dystrophin expression or mitigating disease progression. Special emphasis is placed on the importance of early diagnosis, the utility of genetic screening, and the innovations in pre-and post-natal testing. As the field advances toward personalized medicine, the integration of precision therapies with cutting-edge diagnostic technologies promises to improve both prognosis and quality of life for individuals with DMD. Full article

Cerebral palsy is the leading cause of motor disability in early childhood, with no curative treatment currently available. To mitigate its effects and promote motor rehabilitation, robotic-assisted therapies have emerged as a complement to conventional physiotherapy. In particular, cable-driven exoskeletons offer notable advantages, providing patients with additional mobility and interaction with their environment while preserving motion assistance. Within this context, the Discover2Walk project introduces a modular cable-driven robotic platform designed for early-stage gait rehabilitation. This article presents a novel ankle control module capable of actuating 3 degrees of freedom: 2 translational (in the x and z directions) and 1 rotational (dorsiflexion/plantarflexion). Experimental results confirm the technical feasibility of the approach and its effectiveness in guiding motion within the targeted degrees of freedom. Full article