Search Results (6,008)

Recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) carries a poor prognosis; however, immune checkpoint inhibitors have emerged as critical therapeutic options. Although the KEYNOTE-048 trial established the efficacy of pembrolizumab, the population was restricted to major sites (e.g., oral cavity, oropharynx, hypopharynx, and larynx), excluding subsites such as the paranasal sinuses and nasopharynx. To evaluate outcomes in these populations, we conducted a multicenter retrospective study of 167 patients with R/M SCCHN treated with pembrolizumab between December 2019 and February 2022. The cohort comprised 127 patients with tumors in included sites and 27 in excluded subsites. Primary endpoints included overall survival (OS), progression-free survival (PFS), overall response rate (ORR), disease control rate (DCR), and immune-related adverse events (irAEs). In the excluded subsite group, median OS was 15.2 months (1-year rate: 70.6%), and median PFS was 4.9 months (1-year rate: 21.2%). The ORR was 22.2% and the DCR was 59.3%. The incidence of irAEs was 25.9%, with Grade ≥ 3 events in 3.7%. Survival outcomes did not differ significantly from those in included sites. These findings suggest the potential efficacy and safety of pembrolizumab in subsites excluded from KEYNOTE-048, warranting validation in prospective trials. Full article

Robot-assisted radical prostatectomy (RARP) is the definitive surgical treatment for localized prostate cancer (PCa). Some patients with post-RARP biological recurrence (BCR) eventually develop distant metastases and subsequent PCa-related mortality. The objective of this study was to clarify the predictive factors for the risk of metastatic disease after BCR in patients with PCa who underwent RARP. This multicenter retrospective cohort study was conducted in nine Japanese institutions and enrolled 491 men with BCR, detected between 2011 and 2024. During the median 59-month follow-up period, 44 patients (9.0%) had radiological confirmation of distant metastasis. Patients with developed metastases after BCR exhibited higher biopsy Gleason grade and pathological T stage, increased lymphovascular invasion (LVI) in the surgical specimen, and a shorter interval from RARP to BCR. In univariate analysis, LVI and a time to BCR after RARP of ≤14.9 months were significant predictors of distant metastasis. In the multivariate analysis, LVI constituted a significant independent predictor of distant metastasis (p = 0.011). The 3-year metastasis-free survival (MFS) rates were 85.5% and 94.1% in patients with and without LVI, respectively. The MFS was significantly prolonged in patients with negative LVI compared to those with positive LVI (p = 0.007). In Japanese males with BCR after RARP, LVI was identified as an independent predictor of metastatic progression. Full article

High-grade serous ovarian cancer (HGSOC) is the most prevalent and aggressive form of epithelial ovarian cancer and is characterized by high recurrence rates and poor clinical outcomes. In this study, we identify molecular signatures associated with recurrence by conducting integrative transcriptomic and proteomic analyses on paired primary and recurrent HGSOC tissues from 34 patients. RNA sequencing and proteomic profiling revealed 185 differentially expressed genes (DEGs) and 36 differentially expressed proteins (DEPs) linked to recurrence. Pathway enrichment and Ingenuity pathway analyses highlighted the involvement of immune cell trafficking, cell signaling, and MAPK pathway activation in recurrent tumors. A survival analysis identified seven DEGs that correlated significantly with recurrence-free survival; among them, IL7R, IRF8, and PTPRC were upregulated in recurrent tumors and associated with poor prognosis, and NSG1 was downregulated and linked to favorable outcomes. Immunohistochemistry validated the differential expression of these markers at the protein level. The proteomic analysis demonstrated that recurrent tumor-specific DEGs are functionally linked to MAPK signaling. Co-expression analyses revealed dynamic regulatory interactions between the DEGs and DEPs, suggesting context-dependent molecular shifts during recurrence. This integrative multi-omics approach reveals that key molecular alterations underlie HGSOC recurrence and identifies IL7R, IRF8, PTPRC, and NSG1 as potential prognostic biomarkers and therapeutic targets. Our findings provide a foundation for targeted strategies to improve outcomes for patients with recurrent HGSOC. Full article

Background: Venous thromboembolism (VTE) is still a serious clinical problem because many patients still have a significant chance of having it happen again after their first course of anticoagulation is over. In recent years, reduced-dose direct oral anticoagulants (DOACs) have been investigated as a means to ensure prolonged protection while diminishing the risk of bleeding complications. This systematic review aims to summarize the available evidence comparing reduced-dose and full-dose DOAC regimens during the extended phase of VTE treatment. Methods: A systematic search of PubMed and the Cochrane Library (January 2010–November 2025) identified randomized trials and one ambispective cohort study evaluating reduced-dose apixaban (2.5 mg BID), rivaroxaban (10 mg OD), dabigatran (110 mg BID), or edoxaban (30 mg OD). Methodological quality was assessed using RoB-2 for trials and the Newcastle–Ottawa Scale for observational data. Because of differences in study designs and outcome definitions, a narrative synthesis was applied. Results: Five studies met the inclusion criteria. Across trials, reduced-dose DOACs maintained consistently low rates of recurrent VTE: 1.7% in AMPLIFY-EXT versus 8.8% with placebo; 1.2–1.5% in EINSTEIN CHOICE versus 4.4% with aspirin; 2.2% in RENOVE versus 1.8% with full-dose therapy; and 1.3% in HI-PRO versus 10% with placebo. Real-world data from Valeriani et al. showed only a single recurrence (0.7%) over nearly three years. Major bleeding remained uncommon, ranging from 0.1 to 0.5% in randomized trials and 2.1–2.9% in longer-term observational cohorts. Conclusions: In summary, reduced-dose DOACs appear to offer a favorable balance of safety and efficacy, providing durable protection against recurrence with a lower bleeding burden. These findings support their role as a practical extended-treatment strategy in clinical practice. Full article

Dientamoeba fragilis is a protozoan of the human digestive tract, yet its transmission and pathogenic role remain poorly understood. This study aimed to evaluate its impact on the efficacy and safety of fecal microbiota transplantation (FMT) in treating recurrent Clostridioides difficile infection (rCDI). This longitudinal cohort study analyzed stool samples from FMT donors and recipients pre-treatment and at 2 and 8 weeks post-FMT. All samples were retrospectively tested using real-time PCR. Shotgun metagenomics was also performed on selected donor–recipient pairs to explore transmission. CDI cure rates, gastrointestinal adverse events (AEs), and serious adverse events (SAEs) were assessed prospectively. A total of 53 FMT were analyzed (179 samples), with 23 (43%) derived from D. fragilis-positive donor stool (4 of 10 donors, 40%). Four of 52 recipients (18.2%), initially negative and who received treatment from positive donors, tested positive post-FMT. Shotgun metagenomics could not definitely confirm transmission due to the lack of a good reference genome. No significant differences in efficacy, AE, or SAE were observed between FMT from D. fragilis-positive versus -negative donors, even in immunocompromised patients. No SAEs were attributed to FMT. D. fragilis may be transmitted via FMT without evidence of short-term clinical impact. Consequently, RT-PCR detection should be interpreted cautiously in the context of donor exclusion decisions. Full article

Background: Head and neck (H&N) cutaneous melanomas have poorer outcomes than melanomas at other sites, yet sentinel lymph node biopsy (SLNB)—a key prognostic tool in clinically node-negative disease—is less frequently performed, particularly outside tertiary centers. We evaluated the feasibility and prognostic relevance of SLNB in a medium-volume regional institution. Methods: We retrospectively reviewed patients with primary H&N cutaneous melanoma who underwent SLNB at the Department of Oral and Maxillofacial Surgery, University of Szeged, between 2010 and 2022. Clinicopathological features, nodal outcomes, recurrence patterns, recurrence-free survival (RFS), and overall survival (OS) were analyzed using Kaplan–Meier methods and univariate Cox regression. Results: Thirty-eight patients underwent SLNB, with a 100% sentinel lymph node identification rate and no major complications. Positive sentinel lymph nodes were identified in 8 patients (21.1%). Two false-negative events occurred, resulting in a false-omission rate of 6.7% and a negative predictive value of 93.3%. SLN-negative patients demonstrated longer RFS and OS, although differences were not statistically significant. Among patients with intermediate-risk melanoma (pT1b–pT3a), 18.5% had a positive SLN. Conclusions: SLNB is a safe and clinically meaningful staging procedure for H&N melanoma in a medium-volume regional center. Sentinel node status provides important prognostic information and supports appropriate patient selection for contemporary adjuvant therapy. Full article

Background and Objectives: This study aimed to comparatively evaluate the association of commonly used comorbidity scores with survival, mortality, and recurrence in ovarian cancer patients aged 50 years and above. Materials and Methods: In this single-center, retrospective study, 130 female patients diagnosed between 2017 and 2024 who had received systemic therapy and had complete medical records were included. Comorbidity scores—including the Charlson Comorbidity Index (CCI), Cumulative Illness Rating Scale-Geriatric (CIRS-G), Adult Comorbidity Evaluation-27 (ACE-27), Elixhauser Comorbidity Index, Index of Coexistent Disease (ICED), and Functional Comorbidity Index (FCI)—were calculated for each patient. Survival analyses were conducted using the Kaplan–Meier method and Cox regression modeling. The prognostic accuracy of comorbidity scores was assessed via receiver operating characteristic (ROC) curve analysis. Results: Patients with higher CCI scores had significantly shorter survival, and CCI was identified as an independent prognostic factor in multivariate analysis. While other comorbidity scores were associated with overall survival in univariate analyses, they lost statistical significance in multivariate models. Patients with a higher comorbidity burden experienced more frequent disease recurrence and shorter time to recurrence. Conclusions: Comorbidity burden is a key clinical determinant of survival and disease trajectory in older patients with ovarian cancer. The CCI demonstrated the highest prognostic accuracy in this population and may serve as a valuable tool in individualized treatment planning. Integration of comorbidity-based assessments into standard decision-making processes is recommended in geriatric oncology practice. Full article

Background and Objectives: Bladder cancer (BC) represents a significant global health burden, ranking as the tenth most commonly diagnosed malignancy worldwide, with an incidence rate of 5.6 per 100,000 person-years annually. The research team aimed to summarize evidence on specialized nursing-led interventions for bladder cancer management across the disease continuum. Materials and Methods: This scoping review used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) methodology to search four databases from January 2018 to November 2025. Results: This concise but informative scoping review of 20 studies revealed substantial clinical and patient-reported benefits from specialized nursing interventions. Enhanced recovery after surgery (ERAS) protocols incorporating structured nursing care demonstrated a 35% reduction in postoperative complications. Integrated nursing interventions during postoperative intravesical therapy significantly improved patient satisfaction, treatment compliance, and self-efficacy while reducing anxiety and depression. Digital health platforms, including internet-based and mobile applications, proved effective in reducing caregiver burden, enhancing disease knowledge, and improving coping strategies. Preoperative stoma education and postoperative ostomy care management significantly improved self-efficacy, stoma care knowledge, and overall health-related quality of life. Psychosocial interventions, including cognitive behavioral therapy and mindfulness-based approaches, demonstrated significant improvements in quality of life and reductions in fear of recurrence, depression, and anxiety. However, a critical evidence gap exists regarding bladder cancer-specific mental health interventions. Conclusions: Specialized nursing-led care plays a critical role in strengthening clinical and assistive practice in bladder cancer. Evidence from this scoping review shows that nursing-led interventions significantly improve clinical outcomes, patient satisfaction, symptom management, and quality of life across all phases of bladder cancer care while reducing caregiver burden and enhancing psychological well-being for both patients and families, reinforcing the value of integrating specialized nursing roles into routine bladder cancer management. Full article

Background/Objectives: Diffuse sinonasal exophytic papillomas (DSNEPs) are rare entities, with similarities to recurrent respiratory papillomatosis (RRPs). DSNEP treatment is usually based on surgical excision, but the recurrence rate is high. Bevacizumab injections have been increasingly used as an adjuvant option for RRP, but their role in DSNEP treatment remains unknown. The current study describes the preliminary experience, safety profile, and exploratory outcomes of sublesional bevacizumab injections following surgical excision. Methods: We undertook a retrospective, single-centre study of a cohort of patients diagnosed with DSNEP between 2011 and 2018. All patients were treated with surgical excision and sublesional bevacizumab injections. The effect of bevacizumab was evaluated using a severity score developed to quantify lesion size and the extent of affected areas in each patient. Results: Seven patients diagnosed with DSNEP were treated. All patients were male, with a median age at diagnosis of 42 years [38–44.5]. Human papillomavirus (HPV) DNA was detected in all patients: HPV-11 in six cases (85.7%) and HPV-6 in one case (14.3%). Bevacizumab was injected into the submucosa of their surgical sites. The median follow-up was 55.5 months [40.85–82.73]. Most patients (85.72%) presented recurrence, with a median of 3 years [1.5–4]. A statistically significant reduction in the severity score was observed (p = 0.017), although this finding cannot be attributed solely to bevacizumab due to study design limitations. No relevant complications were reported. Conclusions: Nasal sublesional bevacizumab injections were well tolerated and feasible as an adjuvant approach to DSNEP. Larger prospective studies are needed to confirm its safety and assess its potential benefit. Full article

Background: Complete rectal prolapse (RP) is a debilitating pelvic floor disorder often accompanied by obstructed defecation syndrome (ODS), fecal incontinence, and LARS-like bowel dysfunction. Laparoscopic resection rectopexy (LRR) is an established abdominal approach; however, functional outcomes after LRR with transanal specimen extraction (LRR-TSE) are incompletely defined. Aim: To evaluate short- and long-term functional outcomes—ODS, Wexner incontinence score (WIS), and LARS—in patients undergoing LRR-TSE. Methods: This single-center cohort included 53 consecutive patients who underwent LRR-TSE between January 2013 and December 2019. Variables were prospectively recorded and analyzed retrospectively. ODS, WIS, and LARS scores were assessed preoperatively and at 3, 6, and 12 months. Longitudinal changes were analyzed using repeated-measures ANOVA with Greenhouse–Geisser correction, polynomial contrasts when appropriate, and Bonferroni-adjusted pairwise comparisons. Results: ODS improved significantly over time (p < 0.001), decreasing from 12.8 ± 3.2 preoperatively to 2.4 ± 2.1, 4.2 ± 2.2, and 5.2 ± 2.9 at 3, 6, and 12 months, respectively. LARS scores declined from 18.0 ± 12.7 at 3 months to 8.8 ± 6.8 at 6 months and 3.5 ± 4.2 at 12 months (p < 0.001). WIS showed a transient increase at 3 months (8.1 ± 5.2), followed by improvement at 6 and 12 months (3.2 ± 3.7 and 2.4 ± 3.0; p < 0.001). Sex and body mass index did not affect functional trajectories (p > 0.05), whereas patients aged ≥50 years had higher postoperative LARS and WIS scores (p < 0.05). Complications occurred in 5 patients (9.43%), including one anastomotic leak with a mortality rate of 1.85%. Full-thickness recurrence occurred in 2 patients (3.77%), and 3 developed mucosal prolapse managed with Delorme’s procedure. Conclusions: LRR-TSE is a safe and feasible minimally invasive technique that improves constipation, continence, and LARS-related bowel dysfunction. Early postoperative impairment may overestimate long-term functional severity, highlighting the need for follow-up beyond 12 months. Full article

Liver cancer remains a significant global health challenge, with hepatocellular carcinoma (HCC) being the most prevalent form. Despite advancements in treatment, high recurrence rates and the limited efficacy of conventional therapies highlight the need for novel interventions. Cinobufagin (CB), a bufadienolide extracted from the parotid secretion of Bufo gargarizans and B. melanostictus, has emerged as a promising compound with multiple antitumor mechanisms. This comprehensive review assesses the current evidence regarding CB and its containing medicine, cinobufacini, in liver cancer models. Cinobufacini is a traditional Chinese medicine extract, whereas CB refers specifically to one of its active components. The pharmacodynamic actions of CB include induction of apoptosis, DNA damage, inhibition of proliferation and migration, and modulation of key oncogenic pathways such as PI3K/Akt/mTOR, Akt/ERK, and AURKA-mTOR-eIF4E. Additionally, CB disrupts tumor metabolism and induces oxidative stress. Preclinical studies, both in vitro and in vivo, demonstrate significant antitumor efficacy. However, concerns remain regarding CB’s toxicity profile at high doses. This review emphasizes the therapeutic potential of CB in HCC treatment and advocates for further translational research to optimize its clinical applicability, dosage, and safety. Full article

Background/Objectives: Hidradenitis suppurativa (HS) is a chronic, inflammatory, and recurrent disorder of the pilosebaceous unit with numerous comorbidities. Growing evidence suggests that depression and anxiety occur more frequently in HS patients, yet their relationship with clinical severity and especially subjective symptoms remains insufficiently understood. The aim of this study was to assess the prevalence and severity of probable depressive and anxiety symptoms in Polish patients with HS and to examine their associations with clinical disease severity, pain and itch intensity, and quality of life (QoL). Methods: Eighty-four HS patients were included in this cross-sectional study. Disease severity was assessed using Hurley staging and the IHS4. Pain and itch intensity were evaluated using the Numeric Rating Scale (NRS). Psychological assessment included self-administered screening questionnaires, such as PHQ-9 and HADS-D for depression and GAD-7 and HADS-A for anxiety. QoL was measured using DLQI and HiSQOL instruments. Statistical analyses were performed with p < 0.05 considered significant. Results: Possible depressive disorders were identified in 25.0% of patients. PHQ-9 and HADS-D scores differed significantly across Hurley stages and correlated positively with IHS4. Possible anxiety disorder according to GAD-7 criteria was present in 15.5% of patients. Both GAD-7 and HADS-A correlated with IHS4. They also showed correlations with pain and/or itch intensity. All psychological measures showed strong correlations with both QoL instruments. Conclusions: Depression and anxiety seem to be common in HS and closely associated with clinical severity and reduced QoL. Their relation with pain and itch requires further studies. These findings underscore the need for multidisciplinary management in HS care. Full article

Prostate cancer survivors require coordinated long-term care after treatment. We examined patterns of follow-up care and identified characteristics associated with the frequency of radiation oncology (RO) visits during survivorship. We conducted a population-based cohort study of men diagnosed with prostate cancer between April 2010 and March 2019 in Ontario, Canada, who underwent first-line radiotherapy. Survivorship began three years following radiation. Using a recurrent event framework, we identified demographic and clinical characteristics associated with the rate of RO follow-up. Survivors seeking RO follow-up declined by 46.2% over five years of survivorship. Higher-risk characteristics, such as higher ISUP grade, higher stage, detectable prostate-specific antigen (PSA) score, and receipt of brachytherapy and/or hormones, were associated with more frequent RO visits. For instance, relative to International Society of Urological Pathology (ISUP) Grade 1, those with Grades 3 through 5 experienced follow-up rates that were 20%, 25%, and 34% higher, respectively. Despite concordance between patient risk and rate of RO follow-up, 23.6% of survivors continued to visit their RO providers into their fifth year of survivorship, more than half of whom were ISUP grades 1–2. Primary care follow-up remained stable. While frequency of RO follow-up appropriately reflected patient risk profile, many low-risk survivors still sought long-term RO-led care. This suggests an opportunity to encourage lower-risk prostate cancer survivors to seek follow-up care with their general practitioner. Full article

Desmoplastic small round cell tumor (DSRCT) is a rare but aggressive soft tissue sarcoma of the abdomen. With an asymptomatic course and rapid dissemination, DSRCT’s prognosis is poor at diagnosis. This study characterizes the demographic variation and genomic profile of DSRCT to guide studies into diagnosis and treatment. The AACR GENIE database was utilized to identify genetic alterations in DSRCT. Data was queried to identify disease prevalence by different demographic variables. Information was collected on frequency of somatic mutations and copy number alterations, rates of mutation co-occurrence, and mutations seen in primary and metastatic samples. ARID1A, TP53, ATM, TERT, and FGFR4 were the most frequently identified somatic mutations. Copy number alterations seen in DSRCT were commonly homozygous deletions in tumor suppressor genes. Independent of sex, WT1 mutations were most common. Non-White patients saw single occurrences of many mutations but recurrent ones in ANKRD11 and KMT2C. Co-occurrence was found between FGFR4 and EP300. Moreover, primary tumor samples had exclusive mutations in AKAP9, KDM2B, MAGED1, MKI67, PCLO, and TRAF1. Metastatic samples had exclusive mutations in FIP1L1 and NRIP1. Our data highlights mutational variation across demographic cohorts. These patterns are vital to future studies into identifying diagnostic markers or therapeutic targets. Full article

The incidence of peripheral lung squamous cell carcinoma (p-LUSC) has increased in recent years, but the clinical features of early-stage p-LUSC remain unclear. In the present study, we aim to elucidate the general clinical features of p-LUSC by comparing it with peripheral lung adenocarcinoma (p-LUAD). Patients with p-LUSC or p-LUAD who were at an early imaging stage and underwent complete lobectomy with systematic lymph node dissection were included. The clinical characteristics of p-LUSC were elucidated through comparative analysis with p-LUAD, and independent prognostic factors for recurrence-free survival were identified. A total of 103 patients with p-LUSC and 600 patients with p-LUAD were included. Compared with p-LUAD, all p-LUSC cases appeared as solid nodules (SDNs) on imaging, and p-LUSC was associated with the male sex, older age, smoking history, lobulation sign, interstitial pneumonia, and a shorter volume doubling time. In terms of malignant aggressiveness, p-LUSC demonstrated a significantly lower lymph node metastasis rate than SDNs of p-LUAD in the >2.0 to ≤3.0 cm group, while no statistically significant difference was observed between the two groups in the 0–2.0 cm group. As for prognosis, tumor size and lymph node metastasis were found as independent risk factors for tumor recurrence. Full article