Cancers最新文献

Background/Objectives: The role of female surgeons in urology has been steadily increasing. We performed a contemporary review of American Board of Urology (ABU) case logs focused on oncologic procedures and evaluated the role of female surgeons over the past two decades. Methods: Operative logs from ABU examinees from 2003 to 2023 were analyzed. We identified open-approach (OA) and minimally invasive (MIS) radical nephrectomy (RN), partial nephrectomy (PN), radical nephroureterectomy (RNU), radical prostatectomy (RP), and adrenalectomy (RA) using CPT codes. Total case volumes as well as reported fellowship training were recorded and tabulated. The counts and proportions of OA and MIS procedures were analyzed over time and by surgeon gender. Results: From 2003 to 2023, 54,972 surgical procedures were reported to ABU with only 2.1% (1127) being performed by female surgeons. Of these, 32.5% (366) were OA and 67.5% (761) were MIS. Despite the low overall composition of female-performed procedures, the number of surgeries performed by females increased over time. Among female surgeons, the proportion of MIS surgeries increased over time, from 37.5% to 71.5% in 2003-2009 to 2017-2023, respectively. Females versus males performed comparably for OA for RN and RA; however, females performed more open PN, RNU, and RP than their male counterparts. Moreover, the number of procedures performed by oncology fellowship-trained females increased significantly. Conclusions: Our analysis of over twenty years of data submitted to the ABU indicates that the surgical volume of oncologic procedures by female urologists has been increasing. These findings demonstrate the increased contributions by female surgeons to the field urologic oncology.

Background/Objectives: Hepatocellular carcinoma (HCC) constitutes a leading cause of mortality worldwide. Liver transplantation (LT) and liver resection (LR) represent the main curative-intent treatment modalities for early-stage HCC. LT can offer the advantage of both removing the HCC and alleviating the potential underlying liver disease, yet its application is limited by organ scarcity, waitlist dropout, and eligibility criteria. Hence, LR remains widely used due to greater accessibility but is associated with high recurrence rates. Salvage LT is a treatment option for patients with HCC recurrence post-LR, but up to 40% of patients develop non-transplantable recurrence (NTR), defined as recurrence beyond transplant criteria, which precludes LT and is associated in poor outcomes. Methods: The present review aims to summarize the current state of evidence on the comparison of LT and LR, the management of recurrent HCC, and the risk factors associated with NTR. Results: Clinical and histopathologic factors consistently associated with NTR across studies include larger tumor size, multiple tumors, elevated alpha-fetoprotein levels, underlying liver fibrosis or cirrhosis, microvascular invasion, and satellite nodules-features that reflect aggressive tumor biology and impaired hepatic reserve. Conclusions: Improved preoperative risk stratification and identification of patients at high risk for NTR is essential to inform optimal treatment selection.

Background and Objective: Patients with stage III clear cell renal cell carcinoma (ccRCC) have a high risk for disease recurrence post-nephrectomy. To mitigate overtreatment, there is a pressing need to determine who benefits from immune checkpoint inhibition (ICI) around the time of surgical resection. We performed digital spatial analysis of both gene and protein expression in stage III ccRCC tumors, some of which had preoperative ICI exposure. Methods: Nephrectomy specimens from stage III ccRCC patients were analyzed using the Nanostring GeoMx Digital Spatial Profiler. Differential expression analysis was performed and validated using NCT02210117 trial data to identify genes associated with both ICI and clinical response. A gene score was then generated to predict overall survival in patients from The Cancer Genome Atlas (TCGA). Key Findings and Limitations: In a small cohort of 19 patients, RNA expression significantly differed based on preoperative ICI exposure and recurrence status-CD8+ effector and central-memory T-cell signatures were less prevalent in the treatment-naïve with recurrence group. Three out of four patients with preoperative immune checkpoint inhibition recurred. External validation yielded a four-gene set (GZMK, GZMA, ITGAL, and IL7R), where higher expression levels predicted better overall survival in the TCGA cohort (p = 0.005). Conclusions and Clinical Implications: Preoperative ICI favorably altered the tumor microenvironment to resemble that of treatment-naïve patients without recurrence but did not translate to improved survival. Upon external validation, the genes GZMK, GZMA, ITGAL, and IL7R were modifiable with ICI and associated with improved overall survival. Further investigation is needed to assess if patients with low baseline expression of these genes may benefit from ICI around the time of surgery.

Background/Objectives: In order to develop a comprehensive understanding of gastric-type endocervical adenocarcinoma (GEA), an increasingly prevalent HPV-independent cervical cancer, we summarized clinicopathological information and performed prognostic analysis. Methods: A total of 182 patients diagnosed with GEA at our center during the period 2014-2025 were included in this study. Nineteen GEA cases, 6 HPV-independent non-GEA cases, 59 HPV-associated usual endocervical adenocarcinoma cases, and 66 squamous cell carcinoma cases from online database were also included. Results: Vaginal bleeding (39.56%) and watery discharge (35.16%) were the most common symptoms. As many as 21.43% of patients had no specific complaints, and 80% of GEA showed no distinct mass through gynecological examination. A total of 64% of GEA were stage IIB-IV at diagnosis, with a 5-year survival of 41% versus 85% for stage I-IIA (p < 0.05). The rate of lymphovascular space invasion (LVSI), lymph node metastasis, and ovarian metastasis were 49.64%, 42.00%, and 29.29%, respectively. The 5-year survival and recurrence rates after primary therapy were 57% and 23%, respectively. For GEA treatment, surgery might be associated with improved overall survival for the population at stage III-IV. Survival analysis identified deep infiltration depth (≥2/3), a maximum diameter of the tumor (MDOT) of ≥3 cm, and ovary metastasis as potential indicators of worse OS and PFS for whole patients. Additionally, ovary metastasis indicated poor PFS and OS for stage I-II. Genomic information TP53 mutation, PTEN deletion and STK11 mutation might be the most prevalent genomic alterations. Conclusions: These findings indicated GEA as an aggressive cervical cancer, with high rate of lymph node metastasis, high recurrence rate and short 5-year survival. Ovary metastasis reflected advanced disease burden and surgery might be associated with improved survival in advanced stage. For genomic information, GEA showed genetic heterogeneity and a low level of genomic instability.

Background/objectives: Despite significant advances in imaging technology, real-time intra-fraction monitoring of moving targets remains a challenge in markerless radiotherapy. This retrospective study investigates the use of ExacTrac Dynamic by Brainlab as an intra-fraction monitoring tool for stereotactic body radiotherapy (SBRT) in both early-stage NSCLC and oligometastatic disease.

Methods: A total of 63 X-ray pairs from 21 patients were analyzed to evaluate tumor visualization with and without a surrogate approach. Statistical analysis was conducted to determine whether failures could be attributed to tumor size or localization using the Mann-Whitney U-test and Fisher's exact test. The accuracy of the X-ray/digitally reconstructed radiograph (DRR) surrogate-based fusion was assessed by calculating and comparing the corresponding 3D vectors according to the linear mixed effects model, with a random slope effect for size of surrogate and a random intercept per patient.

Results: Surrogates enhanced tumor visualization on X-ray/DRR fusions from 14.3% to 75.5%. Tumor size and lung affected (left or right) did not predict visualization success. Tumor location, however, tended to influence visibility, with lesions in the upper lobes being more readily visualized (88%) than those in the lower lobes (48.1%), although no statistical significance was reported (p > 0.05). Regarding geometric accuracy, 76% of the analyzed data points deviated less than 5 mm in the 3D vector measurements, the mean values were around 4 mm (±3 mm), and the medians were within 3 mm across all conditions. No statistically significant differences (p > 0.05) were found based on the surrogate size or the triggering time of the X-ray during the breathing cycle.

Conclusions: Surrogate-based DRRs, referred to as Correlation Objects, demonstrate consistent geometric accuracy across multiple surrogate sizes and X-ray acquisitions, supporting the clinical translation of markerless lung targeting workflows for lung SBRT.

Purpose: Hepatobiliary scintigraphy (HBS) provides quantitative assessment of (future remnant) liver function, aiding clinical decision-making for surgical resection and radioembolization of hepatocellular carcinoma (HCC). However, its role for thermal ablation remains unexplored. This pilot study aimed to explore the potential role of HBS in guiding patient selection and risk stratification for thermal ablation. Methods: All HCC patients who underwent thermal ablation between January 2021 and August 2025 and had HBS performed prior to ablation were retrospectively reviewed. Ablated non-tumor liver volumes (i.e., volume of ablated healthy parenchyma) were quantified using 3D segmentation. Absolute ablated liver function (i.e., the proportion of total HBS-derived liver function ablated) was also assessed. Clinical outcomes included changes in clinical scores (e.g., Child-Pugh) and the occurrence of hepatic decompensation after ablation. Results: Nine patients (13 tumors) were included. Median global HBS-derived liver function was 3.2%/min/m² (range 1.6-6.8%/min/m²). Three patients developed hepatic decompensation > 3 months after ablation, unlikely related to thermal ablation itself. The patient with the lowest baseline function (1.6%/min/m²) tolerated ablation without hepatic decompensation. Median ablated non-tumor liver volume was 14.4 cm³ (range 3.1-46.7 cm³), corresponding to a median of 0.9% (range 0.2-3.6%) of total liver volume ablated per lesion. Median absolute ablated function was 0.05%/min/m² (range 0.02-0.21%/min/m²). Conclusions: Thermal ablation was feasible and well tolerated even in patients with severely impaired liver function. Routine pre-ablation HBS does not appear necessary for thermal ablation of HCC, as only a small percentage of total functional liver volume is ablated.

Background: Female patients undergoing radical cystectomy (RC) for bladder cancer have historically presented with more advanced disease and poorer survival outcomes than males. These disparities have been attributed to biological differences, delayed diagnosis, and variations in treatment delivery. Recent data suggest, however, that outcomes may converge when patients are managed in standardized, multidisciplinary, high-volume centers. This study evaluated the influence of gender on perioperative features and oncological outcomes such as disease-free survival (DFS), disease-specific survival (DSS), and overall survival (OS) at a tertiary uro-oncology center.

Methods: We retrospectively reviewed a prospectively maintained database of patients who underwent open or robotic-assisted RC for histologically confirmed urothelial carcinoma between 2014 and 2023 at Guy's and St. Thomas' NHS Foundation Trust. Demographic, perioperative, and pathological variables were stratified by gender to assess their association with DFS, DSS, and OS.

Results: A total of 887 patients were included: 640 men (72.2%) and 247 women (27.8%), with similar mean age (68.5 vs. 68.1 years) and tumour histology (pure urothelial carcinoma 85% vs. 83%). Men had a higher prevalence of diabetes and chronic kidney disease, but no significant differences were observed in time from referral to surgery (0.93 vs. 1.03 months, p = 0.93), use of neoadjuvant therapy (21.6% vs. 17.3%, p = 0.25), or surgical approach (p = 0.55). Pathological stage distribution was comparable between sexes (pT0-1: 44% vs. 50%; pT2-4: 56% vs. 50%; p = 0.13). Kaplan-Meier analysis revealed no significant gender-related differences in 12-month DFS (77.3% vs. 75.4%, p = 0.20), DSS (85.6% vs. 86.9%, p = 0.56), or OS (81.2% vs. 85.2%, p = 0.70).

Conclusion: In this high-volume tertiary center, gender did not independently influence perioperative or survival outcomes following radical cystectomy. These findings suggest that standardized, multidisciplinary management within specialized bladder cancer pathways may mitigate the pathological and survival disparities historically associated with gender.

Non-small cell lung cancer (NSCLC) represents over 80% of all lung cancer cases and still has a huge mortality worldwide. Targeting epidermal growth-factor receptor (EGFR) alterations with overall response rates of more than 80% has provided a paradigm shift in the treatment of NSCLC; however, NSCLC patients harbouring uncommon mutations and exon 20 insertions still have a dismal prognosis underscoring the urgent need to develop novel EGFR tyrosine kinase inhibitors (TKIs) with proven activity against these EGFR alterations. Zipalertinib is a newly developed oral, irreversible compound which is characterized by its unique pyrrolopyrimidine structure which discriminates this novel TKI from others. It is active against the classical mutations (i.e., del19, L858R) and some of the uncommon mutations (e.g., T790M, G719X, S768I, L861Q, but not C797S) and is predominantly active in NSCLC cells harbouring exon20ins. Zipalertinib is currently being extensively evaluated in several clinical NSCLC trials (REZILIENT 1-4) and has shown significant clinical activity in NSCLC patients with uncommon mutations, exon20ins, and in brain metastases (REZILIENT 3 trial). Moreover, zipalertinib in combination with platinum-based chemotherapy followed by zipalertinib monotherapy as first-line therapy is currently being evaluated in the pivotal, ongoing REZILIENT 3 randomized trial. In addition, the efficacy of zipalertinib is also studied in the adjuvant setting (REZILIENT 4 trial, stage IB-IIIA NSCLCs with exon20ins and uncommon mutations). The role and the integration of therapies targeting exon20ins or uncommon mutations into the first- and second-line treatment armamentarium for NSCLC patients is not yet fully established, and the therapeutic impact of monotherapies (e.g., sunvozertinib, firmonertinib) versus combinations with standard platinum-based chemotherapy (e.g., zipalertinib, amivantamab) currently still lacks robust evidence to further change the therapeutic landscape for these patients. Therefore, results from the ongoing trials are eagerly awaited and are expected to shed some light on these open questions.

Despite a thorough understanding of the structure of human papillomavirus (HPV) and its genotypic variations (high-risk and low-risk variants), the mechanisms underlying HPV-induced cervical cancer (CC) pathogenesis and the molecular signatures of drug resistance remain to be fully understood. Accumulating evidence has shown the involvement of kinase targets in the induction of drug resistance in high-risk (HR) HPV-CC. Molecularly, the genome of high-risk HPV is reported to control the expression of host kinases. In particular, Aurora kinases A, B, and C (ARKA, ARKB, and ARKC), phosphotidylinositol-trisphosphate kinase (PI3K)-Akt, and Glycogen synthase kinase3-α/β (GSK3 α/β) promote the transformation of infected cells, and also enhance the resistance of cells to various chemotherapeutic agents such as nelfinavir and cisplatin. However, the precise mechanisms through which HPV activates these kinases are yet to be fully elucidated. Furthermore, there is still ambiguity surrounding whether targeting HPV-induced kinases along with HPV-targeted therapies (such as phytopharmaceuticals and PROTAC/CRISPR-CAS-based systems) synergistically inhibit cervical tumor growth. Given the critical role of kinases in the pathogenesis and treatment of CC, a comprehensive review of current evidence is warranted. This review aims to provide key insights into the mechanisms of HPV-induced CC development, the involvement of kinases in drug resistance induction, and the rationale for combination therapies to improve clinical outcomes.

Background/objectives: Trace metals, including copper (Cu) and zinc, are associated with the development and prognosis of hepatocellular carcinoma (HCC). However, their interference with magnetic resonance imaging (MRI) limits their use as potential biomarkers. This study investigated the usefulness of Synchrotron Radiation-excited X-ray Fluorescence (SR-XRF) imaging in studying the distribution of trace metals in HCC.

Methods: This case-control study analyzed 33 specimens from 32 patients with HCC who underwent surgical resection (n = 29) or biopsy (n = 3) at Kobe University Hospital between December 1999 and November 2002. The findings of SR-XRF were compared with those of MRI and histopathology.

Results: SR-XRF provided two-dimensional mapping of trace metal distribution with high spatial resolution (1.0 µm). The mean tumor-to-liver ratio (TLR) of Cu content was significantly higher in well-differentiated HCCs than in moderately and poorly differentiated HCCs (p < 0.05). Moreover, the mean TLRs of Cu content were significantly higher in high-intensity lesions than in iso- or low-intensity lesions on T1-weighted imaging (p < 0.05).

Conclusions: This study supports previous evidence of the involvement of Cu in HCC development, suggesting its potential as a clinical biomarker for diagnosis and disease progression. Additionally, the results demonstrate that SR-XRF has potential for clinical application due to its ability to map trace metal distribution at high resolution. These findings suggest, rather than demonstrate, the association among Cu accumulation, tumor differentiation, and MRI signal characteristics.