Nasopharyngeal carcinoma (NPC) is a geographically prevalent malignant mucosal tumor endemic to southern China and Southeast Asia. Radiotherapy constitutes the core curative treatment for NPC, often combined with chemotherapy or targeted therapy in clinical practice. Hearing loss is a common radiotherapy-related complication caused by radiation damage to middle ear structures, inner ear cells and auditory nerves, with a variable incidence affected by treatment protocols and patient characteristics. Such auditory dysfunction negatively impacts patients' cognition, emotion and quality of life. However, systematic summaries of subjective evaluation tools and targeted non-surgical rehabilitation strategies for radiotherapy-induced hearing impairment remain insufficient. Accordingly, this review aims to elaborate on the classification, multidimensional clinical impacts, subjective assessment scales, and non-surgical interventions of radiotherapy-related hearing loss, so as to provide evidence-based references for clinical rehabilitation of NPC survivors.
Breast cancer (BC) represents one of the most frequently occurring malignancies and a primary cause of cancer-associated mortality among women globally. AXL, a receptor tyrosine kinase of the TAM family, and signal transducer and activator of transcription 3 (STAT3) are both aberrantly activated in BC and contribute to tumor progression. The present study aimed to investigate the functional association between AXL and STAT3 activation in BC. It was found that the overexpression of AXL in MCF7 and 293T cells enhanced STAT3 phosphorylation and transcriptional activity, whereas AXL knockdown using short hairpin RNA or pharmacological inhibition with R428 suppressed STAT3 activation. AXL overexpression also enhanced the secretion of IL-6, a major upstream activator of STAT3. Bioinformatics analysis of clinical BC datasets (GSE102484, GSE9893 and The Cancer Proteome Atlas) validated a positive correlation between AXL expression and STAT3 signaling activation. Collectively, these findings demonstrate that AXL is associated with STAT3 activation in BC, providing insight into the molecular pathways driving BC progression and uncovering candidate therapeutic targets.
Blood cell count ratios are useful prognostic indicators in cancer. The present retrospective study evaluated the levels of the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and lymphocyte-to-monocyte ratio (LMR) across different treatment phases and their potential prognostic value in nasopharyngeal carcinoma. A total of 99 patients were treated with induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT). Biomarkers were assessed at three separate time points: Pre-IC, pre-CCRT and post-radiation therapy (RT). Results indicated that the NLR and PLR values were higher, while the LMR values were lower at later chronological time points, particularly post-RT. Post-RT, higher NLR and PLR levels and a lower LMR level were observed in non-survivors. Being ≥60 years old was associated with lower odds of elevated PLR post-RT and experiencing weight loss ≥7.5% predicted increased NLR post-RT. Elevated pre-IC and post-RT PLR was associated with reduced 5-year overall survival. Multivariate analysis, although limited by the small number of events (n=15), identified PLR pre-IC and advanced nodal stage (N3) as independent mortality predictors. PLR pre-IC and N3 stage may therefore serve as preliminary independent predictors of poor prognosis, supporting the use of inflammatory biomarkers for risk stratification. Despite this, prospective external validation in larger cohorts is required.
The present study compared the efficacy and safety of non-intubated video-assisted thoracoscopic surgery (NIVATS) with intubated video-assisted thoracoscopic surgery (IVATS) for lobectomy in the treatment of lung cancer through a systematic review and meta-analysis. A total of six electronic databases were searched for studies comparing NIVATS and IVATS published up to October 2024. After rigorous screening and quality assessment, perioperative outcomes and postoperative complications were systematically analyzed from 18 studies, comprising three randomized controlled trials, six propensity score-matched studies and nine retrospective studies. A total of 2,313 patients with lung cancer underwent thoracoscopic lobectomy, of whom 1,082 underwent NIVATS and 1,231 underwent IVATS. The results revealed that NIVATS significantly reduced operative time [mean difference (MD)=11.02; 95% confidence interval (CI), -18.78 to -3.27], lymph nodes harvested (MD=-0.67; 95% CI, -1.24 to -0.11), anesthesia waking time (MD=-22.88; 95% CI, -33.13 to -12.64), feeding time (MD=-4.53; 95% CI, -5.74 to -3.32), chest tube indwelling time (MD=-0.68; 95% CI, -1.16 to -0.21) and hospital stay (MD=-1.16; 95% CI, -1.57 to -0.74) compared with the IVATS group. Total complications [odds ratio (OR)=0.53; 95% CI, 0.31 to 0.90], particularly sore throat (OR=0.18; 95% CI, 0.10 to 0.33) and pneumonia (OR=0.54; 95% CI=0.30 to 0.98) were significantly lower in the NIVATS group than in the IVATS group. Re-intubation occurred in 4.33% of NIVATS patients, while conversion to thoracotomy rates were similarly low in the NIVATS (0.69%) and IVATS (0.60%) groups. Importantly, NIVATS was associated with significantly improved overall survival [hazard ratio (HR)=0.63; 95% CI, 0.40 to 0.98] and recurrence-free survival (HR=0.62; 95% CI, 0.46 to 0.85). No significant differences were observed for anesthesia time, blood loss, hoarseness, air leakage or arrhythmia. Under the enhanced recovery after surgery framework, NIVATS appears to be a safe and technically feasible alternative to IVATS, with the potential to improve patient outcomes based on the available evidence. Its clinical adoption is supported by the evidence in the present study, offering a basis for informed decision-making.
Autotaxin (ATX) lysophospholipase D has been identified as an 'autocrine motility factor' for tumour cells. The tumour microenvironment (TME) serves a critical role in cancer development, with ATX, as a component of the ATX/lysophosphatidic acid (LPA) axis, integrated into a complex network of molecular signalling. This axis is particularly significant because it activates multiple overlapping signal transduction pathways, thereby mediating pleiotropic effects across nearly all cell types within the TME. The ATX/LPA pathway has multiple molecular and cellular drivers, making the signalling mechanisms activated by ATX/LPA an interesting subject for evaluation in cancer development. The present review discusses the multiple effects of ATX/LPA on three macroevents involving several TME components: i) Inflammation and immunity; ii) cellular proliferation and metabolism; and iii) invasion and metastasis. The aim of the present review was to highlight the clinical impact of the ATX/LPA pathways in the pathogenesis of cancer. Clarifying the role of ATX and blocking this pathway in the inflammatory cycle may open novel therapeutic avenues to improve cancer treatment. Although several reviews have addressed the ATX/LPA axis in cancer, most have focused primarily on its roles in tumour growth, migration and metastasis. By contrast, the present review provides an updated, integrative perspective that emphasizes recent advances (2020-2025) regarding the role of the ATX/LPA axis in shaping the immunometabolic landscape of the TME, with particular attention to inflammation-driven immune regulation.
Low-grade serous ovarian cancer (LGSOC), a rare subtype of epithelial ovarian cancer, is characterized by indolent growth and limited chemosensitivity. However, data from low- and middle-income countries are limited. The present study aimed to describe the clinical and pathological characteristics of patients with LGSOC in Indonesia. This retrospective multicenter study was conducted at nine tertiary cancer centers across seven provinces, and included patients with histologically confirmed LGSOC diagnosed according to the 2020 World Health Organization Classification of Female Genital Tumors between January 2019 and December 2024. Demographic, clinical, surgical, pathological and treatment data were extracted from medical records. Recurrence was classified as early (<6 months) or late (≥6 months) after completion of primary treatment. Associations between clinicopathological variables and outcomes were analyzed using Fisher's exact test. Kaplan-Meier (KM) survival analysis with log-rank testing and Cox proportional hazards regression were performed, with a restricted multivariate model to minimize overfitting due to limited events. A total of 160 patients (median age, 46 years; range, 17-75 years) were included, with a median follow-up of 24 months. Of the cohort, ~50% presented with advanced-stage disease (International Federation of Gynecology and Obstetrics III-IV, 50%). Ascites and elevated cancer antigen-125 levels were observed in 43.1 and 70.6% of patients, respectively. Primary debulking surgery was performed in 90% of cases, achieving optimal cytoreduction in 72.5%. The overall recurrence rate was 10, and 92.5% of patients were alive at the last follow-up. KM analysis showed worse survival in patients with advanced-stage disease and residual disease. In univariate Cox regression, residual disease (HR, 7.93) and recurrence (HR, 10.06) showed the strongest associations with mortality. In multivariate analysis, only residual disease remained an independent predictor (adjusted HR, 5.59; P=0.013). In this multicenter cohort, residual disease was the key determinant of survival, underscoring the importance of complete cytoreductive surgery and early diagnosis.
Glioblastoma cells strongly express the tryptophan-metabolizing enzyme indoleamine 2,3-dioxygenase 1 (IDO1), which is important in enabling immune evasion. Notably, glioma stem-like cells (GSCs) express higher levels of IDO1 than differentiated glioblastoma cells (DGCs); therefore, it was hypothesized that IDO1 inhibition in GSCs may induce differentiation. The present study used the glioblastoma cell line U-87MG, and newly established GSC lines 0125-GSC and 0222-GSC. A model GSC line, Rev-U-87MG, was created by culturing U-87MG in serum-free medium. Rev-U-87MG-IDO(-) was generated by continuous treatment with an IDO1 inhibitor. The DGC lines 0125-DGC and 0222-DGC were derived by culturing 0125-GSC and 0222-GSC in serum-containing medium. IDO1-inhibited GSC lines 0125-GSC-IDO(-) and 0222-GSC-IDO(-) were generated by continuous IDO1 inhibitor exposure. The expression levels of IDO1 and stem cell markers (Nestin, Nanog and Sox2) were measured by western blotting, and temozolomide sensitivity was evaluated by cell counting. Notably, U-87MG, 0125-DGC and 0222-DGC adhered without sphere formation. By contrast, Rev-U-87MG, 0125-GSC and 0222-GSC formed spheres, whereas IDO1-inhibited cells showed partial adhesion with reduced sphere formation. IDO1 and stem cell marker expression were reduced in all IDO1-inhibited cell lines. Rev-U-87MG exhibited decreased temozolomide sensitivity compared with U-87MG, whereas Rev-U-87MG-IDO(-) showed increased sensitivity. Similarly, 0125-DGC and 0222-DGC were more sensitive than their parent GSC lines, and 0125-GSC-IDO(-) and 0222-GSC-IDO(-) also exhibited enhanced drug sensitivity compared with their parent GSC lines at multiple concentrations. These findings suggest that IDO1 inhibition may induce the differentiation of GSCs and reduce their resistance to temozolomide.
Pulmonary carcinoid (PC) tumors are rare, well-differentiated neuroendocrine neoplasms of the lung with indolent progression and limited therapeutic consensus in advanced stages. While surgery remains the mainstay for localized disease, optimal management strategies for progressive or unresectable cases remain debated. A case of a 56-year-old man diagnosed with a left upper lobe PC was presented. Initial treatment consisted of platinum-based chemotherapy followed by traditional Chinese medicine. Upon disease progression, he received thoracic radiotherapy, achieving transient stabilization. However, subsequent radiologic surveillance revealed enlargement of mediastinal lymph nodes, prompting the initiation of a triple-modality systemic regimen comprising lobaplatin, the PD-1 inhibitor sintilimab, and the antiangiogenic agent anlotinib. After two treatment cycles, follow-up imaging demonstrated marked lymph node regression with satisfactory tolerability. This case highlights the potential therapeutic value of integrating chemotherapy, immunotherapy and antiangiogenic therapy in advanced PCs, particularly when standard surgical approaches are unfeasible. Although randomized data remain scarce, experience suggests that multimodal systemic therapy may offer disease control in selected patients. Further prospective studies are warranted to refine treatment paradigms for this uncommon malignancy.
Occult breast cancer (OBC) is a rare condition presenting with axillary or distant lymph node metastases without a detectable primary tumor. Immune checkpoint inhibitors (ICIs) show promise in triple-negative breast cancer (TNBC) treatment; however, their efficacy in OBC remains unclear. The present study describes the case of a 71-year-old woman who presented with left cervical and axillary lymphadenopathy. 18F-fluorodeoxyglucose positron emission tomography-computed tomography (CT) and breast ultrasonography revealed no detectable primary breast lesion. Core needle biopsy of the axillary lymph node confirmed the diagnosis of TNBC (estrogen receptor, 0%; progesterone receptor, 0%; human epidermal growth factor receptor 2 score, 0). The programmed death-ligand 1 combined positive score was >10. Since the patient had stage IV disease with the biological subtype defined by lymph node biopsy, breast magnetic resonance imaging was not performed to avoid delaying systemic therapy. Pembrolizumab (Pembro) combined with gemcitabine and carboplatin was initiated. However, the patient developed a Grade 1 rash after the first cycle and diarrhea after the second cycle, followed by immune-related colitis requiring hospitalization. Notably, the emergence of immune-related adverse events (irAEs) paralleled a marked treatment response, with non-contrast CT after three cycles showing complete resolution of left axillary lymph node metastases. Pembro was discontinued, and the patient has maintained a complete response on eribulin monotherapy for >1 year. The present case suggests an association between irAEs and the clinical effectiveness of ICIs, highlighting the potential of Pembro-containing chemotherapy for OBC treatment, and emphasizing the importance of prompt irAE recognition and management. Lymph node-dominant disease may represent a particularly immunogenic context for ICI therapy.
Optimal first-line treatments for RAS wild-type metastatic colorectal cancer (mCRC) remain uncertain, despite the availability of numerous targeted therapies. Direct comparisons between all available regimens are limited, necessitating indirect evidence synthesis. A systematic review and network meta-analysis of randomized controlled trials (RCTs) comparing first-line treatments for RAS wild-type mCRC was conducted in the present study. MEDLINE/PubMed, Embase, Cochrane Central Register of Controlled Trials and Web of Science were searched from inception to September 2025. Primary outcomes included overall survival (OS) and progression-free survival (PFS), while secondary outcomes included objective response rate (ORR) and safety profiles. Random-effects network meta-analyses were performed and treatments were ranked using P-scores. In total, 15 RCTs involving 6,298 patients and seven primary treatment nodes were included. The network demonstrated high levels of consistency for OS (I2=0%) and moderate heterogeneity for PFS (I2=44.8%) and ORR (I2=40.9%). For OS, both cetuximab + chemotherapy [hazard ratio (HR)=0.853; 95% CI: 0.775-0.938; P=0.001] and panitumumab + chemotherapy (HR=0.855; 95% CI: 0.738-0.992; P=0.038) exhibited statistically significant superiority compared with bevacizumab + chemotherapy. Cetuximab + chemotherapy ranked highest for OS (P-score=0.814) and PFS (P-score=0.914). Subgroup analysis demonstrated a pronounced tumor sidedness effect. Anti-EGFR therapy provided a 25.0% reduction in OS risk for left-sided tumors (HR=0.750; 95% CI: 0.672-0.836; I2=0%), whereas no survival benefit was observed for right-sided tumors (HR=1.097; 95% CI: 0.909-1.325). Anti-EGFR regimens were associated with higher rates of grade ≥3 toxicities, reaching up to 83.3%, compared with bevacizumab-based regimens, which fell between 23.4-68.3%. In the present sensitivity analysis, UDP glucuronosyltransferase family 1 member A1-guided bevacizumab + 5-fluorouracil, leucovorin and irinotecan demonstrated favorable outcomes, with OS and PFS P-scores of 0.932 and 0.992, respectively; however, these findings were derived from a single trial with limited comparability. Overall, anti-EGFR antibodies combined with chemotherapy demonstrated consistent and statistically significant survival benefits as first-line treatment for RAS wild-type mCRC, with cetuximab + chemotherapy ranking as the optimal regimen. Treatment benefit from anti-EGFR therapy was markedly influenced by primary tumor location, with notable benefit observed in left-sided tumors and no benefit in right-sided tumors. These findings support tumor sidedness-guided treatment selection in clinical practice, favoring anti-EGFR-based therapy for left-sided and bevacizumab-based therapy for right-sided RAS wild-type mCRC.
The submental arterial island flap (SMIF) is used mostly for closing defects in the oral cavity, but also has its uses for oropharyngeal reconstruction. Since the duration of surgery is shorter compared with that for free flaps, it appears to be a good option for patients with severe anesthesiological risk factors. Therefore, the present study evaluated the functional and oncological outcomes of reconstructing defects after oropharyngeal carcinoma resection with a SMIF in these patients. A total of 10 patients underwent resection of lateral oropharyngeal carcinoma and ipsilateral neck dissection with closure of the defects using a SMIF. Oncological evaluation consisted of endoscopic and radiological standard-of-care restaging, while functional evaluation included a phoniatric swallowing examination with penetration-aspiration scale-score 6 months after surgery. All patients had T2 or T3 carcinoma, while 7 out of 10 patients had nodal involvement. Additionally, 7 out of 10 patients exhibited p16 expression. Pathological clear margins could be achieved in all patients. In all patients, no local, regional or distant recurrence occurred (median follow-up time, 26 months; range, 12-33 months). All patients had complete oral intake with their feeding tubes removed, with 1 patient restricted to dysphagia diet. Despite the severe comorbidities, there were no surgery-related or anesthesia-related complications. One patient who refused the recommended postoperative radiation developed enoral hair growth requiring regular trimming to avoid dysphagia. The SMIF is a reliable flap for reconstruction of lateral oropharyngeal defects with good oncological and functional outcomes. The reduced anesthesia duration appeared to be beneficial for patients with severe cardiac or pulmonary comorbidities. Male patients should be selected to undergo postoperative radiation to prevent enoral hair growth.
Surgical resection remains the cornerstone of the standard therapy for glioblastoma (GBM), yet postoperative recurrence remains a major clinical challenge. Intraoperative photodynamic detection (PDD) using 5-aminolevulinic acid (5-ALA) improves the precision of tumor removal. However, a subset of tumor cells can evade fluorescence-based detection, potentially contributing to residual disease and relapse. The present study analyzed the relationship between cellular migratory capacity and 5-ALA PDD visibility using six patient-derived GBM cell lines (KBT#12137, KBT#10135, KBT#10170, PDM19, PDM22 and PDM123). This study revealed a positive correlation, indicating that cells with higher migratory potential accumulated lower levels of 5-ALA-induced protoporphyrin IX and were therefore more likely to escape intraoperative detection. Transcriptomic profiling identified gene expression signatures specifically associated with this phenotype, highlighting pathways related to cytoskeletal regulation, heme metabolism, and transporter activity. These findings suggest that the migratory potential and diagnostic evasion are functionally linked through shared molecular programs, thereby providing a potential basis for identifying predictive biomarkers associated with incomplete resection and recurrence risk. Overall, this study provides insights that may contribute to improved intraoperative strategies and targeted therapeutic approaches for GBM.
The paradigm of cancer biology has shifted to recognize tumor as a complex ecosystem inhabited by a diverse microbiome. Beyond mere association, the molecular mechanisms driven by microbial virulence factors are critical for understanding how these microorganisms contribute to malignancy. The present review describes a virulence factor-centric framework to deconstruct the microbial 'toolkit' and illustrate its role in enabling the Hallmarks of Cancer. The major classes of virulence factors were systematically analyzed, detailing how each contributes to tumor progression. It was described how bacterial adhesins (for example, Fusobacterium adhesin A and Fap2) initiate oncogenic signaling and mediate immune evasion; how secreted toxins drive genomic instability (Colibactin and CDT) and corrupt cellular signaling pathways (CagA and Bacteroides fragilis toxin); how degradative enzymes (gingipains and collagenases) dismantle the extracellular matrix to facilitate physical invasion; how viral oncoproteins (Human Papillomavirus E6/E7 and Epstein Barr virus latent membrane protein 1) hijack core cell cycle machinery; and how microbial structural components (lipopolysaccharides and extracellular vesicles) and metabolites (secondary bile acids) sustain a pro-tumorigenic environment. This analysis reveals a pattern of functional convergence, where diverse microbial agents repeatedly target core host pathways such as NF-κB, Wnt/β-catenin and p53. This mechanistic understanding reframes the microbiome as an active orchestrator of malignancy and reveals a new frontier of therapeutic targets. Strategies aimed at neutralizing specific virulence factors or modulating the tumor ecosystem represent a novel and promising pillar in oncology.
Secretory carcinoma (SC) is a rare salivary gland neoplasm characterized by the ETV6::NTRK3 gene fusion, and it has been recognized as a distinct entity in the World Health Organization Classification of Head and Neck Tumors since 2017. Case 1 involved a 21-year-old Japanese man who presented with a 1-year history of a slow-growing, painless mass in the right parotid gland. Ultrasonography and magnetic resonance imaging demonstrated a well-circumscribed, homogeneous tumor measuring 16x12x10 mm. The patient underwent superficial parotidectomy. Case 2 involved a 79-year-old Japanese man who noticed a mass in the right parotid region 3 weeks before presentation. Imaging studies revealed a tumor with irregular margins and heterogeneous internal features, measuring 21x16x15 mm. The patient underwent total parotidectomy with selective neck dissection. Histological examination revealed features consistent with SC in both cases. Immunohistochemically, the tumor cells were positive for S-100 protein, mammaglobin and cytokeratin 7. The diagnosis was further supported by detection of the ETV6::NTRK3 gene fusion using reverse transcription-polymerase chain reaction and Sanger sequencing. Both patients received postoperative radiotherapy at a total dose of 60 Gy. No evidence of local recurrence or distant metastasis has been observed during the follow-up period of 7 years in case 1 and 3 years in case 2.
Intraductal papillary mucinous neoplasm (IPMN) is the second most common pancreatic tumour and a common precursor lesion of invasive carcinoma. Tuft cells are chemo-sensory epithelial cells present in the gastrointestinal and respiratory tracts that serve roles in response to infection and tissue repair. In addition, tuft cells have pivotal roles in the carcinogenesis of pancreatic ductal adenocarcinoma (PDAC), especially in tumour suppression, by producing prostaglandin (PG)D2; however, their role in IPMN remains unclear. The present study aimed to evaluate the presence of tuft cells producing PGD2 in human IPMN. Consecutive patients with IPMN who underwent surgical resection were retrospectively enrolled. Dual immunohistochemical staining for POU domain class 2 transcription factor 3 (POU2F3), as a specific tuft cell marker, and haematopoietic PGD synthase (H-PGDS), as a useful marker for PGD2 production, were performed. The present study included 21 patients with IPMN (11 women and 10 men; median age, 74 years). A total of 11, two and eight patients had IPMN with low-grade dysplasia, high-grade dysplasia and associated invasive carcinoma, respectively. POU2F3-positive tuft cells were noted in IPMN, and 20.0% of POU2F3-positive cells in IPMN without invasive carcinoma and the non-invasive regions of IPMN-associated invasive carci-noma expressed H-PGDS. Moreover, POU2F3-positive tuft cells and the ratio of H-PGDS expression in POU2F3-positive tuft cells were significantly lower in the invasive regions than in the non-invasive regions of IPMN-associated invasive carci-noma. These results indicated that POU2F3-positive tuft cells have possible roles in the tumourigenesis of IPMN, as well as in the carcinogenesis of PDAC, because tuft cells present in non-invasive IPMN may serve tumour-suppressive roles via production of PGD2and they were absent in the invasive carcinoma component. Notably, further analyses are required to clarify the role and importance of POU2F3-positive tuft cells in IPMN, which will lead to a better understanding of the pathogenesis of this tumour.
Volumetric modulated arc therapy (VMAT) is an advanced radiotherapy technique for prostate cancer that improves dose conformity but is often accompanied by early urinary toxicities. Non-invasive biomarkers for predicting such adverse events remain limited. In the present study, a secondary analysis of a public urinary metabolomics dataset (MxP® Quant 500; 630 metabolites) from 11 patients treated with VMAT (76 Gy/38 fractions) was performed. Patients were grouped as patients with urinary toxicities (n=7; Grade 1) and those without (n=4). Patient-level Spearman's rank correlation coefficients (ρ) between the metabolite concentration and fraction number were calculated and summarized within each group. Overlaps in the top 60 positively correlated metabolites and bottom 60 negatively correlated metabolites across groups were identified and assessed using OmicsNet 2.0. Four metabolites [cholesteryl ester 20:4, taurodeoxycholic acid, triglyceride (TG) 18:0_32:2 and TG 18:3_34:1] were positively correlated in the toxicity group but negatively correlated in controls. Conversely, five metabolites, including phosphatidylcholines (PCs; PC aa C42:2 and PC ae C42:1), TG 16:0_38:1, fatty acid (FA) 20:2 and diglyceride 18:1_18:1, showed the opposite trend. Network analysis indicated impaired lipolysis, specifically the hydrolysis of TGs into FAs, involving carboxyl ester lipase and adipose TG lipase/hormone-sensitive lipase pathways. One patient with toxicity was on ursodeoxycholic acid, possibly influencing bile acid-related metabolites. Overall, early urinary adverse events in VMAT were associated with lipid metabolism dysregulation. No metabolites remained significant after false discovery rate correction, and this exploratory, hypothesis-generating analysis suggested that urinary metabolomics may serve as a non-invasive biomarker platform for toxicity prediction, warranting validation in larger cohorts.
To explore the value of the ovarian-adnexal reporting and data system (O-RADS) combined with tumor markers, risk of ovarian malignancy algorithm (ROMA) in the differential diagnosis of benign and malignant ovarian-adnexal tumors. A total of 426 patients with 524 cases of ovarian-adnexal tumors confirmed by surgery from January 2021 to January 2024 were included. Ultrasound O-RADS classification, ROMA and their combination were used for differential diagnosis. Taking pathological results as the gold standard, the sensitivity, specificity and the area under the receiver operating characteristic curves were calculated. Among the 524 tumors, there were 104 cases in category 2, 113 cases in category 3, 81 cases in category 4, 226 cases in category 5. The proportions of malignancy in O-RADS categories 2-5 were 0% (0/104), 4.42% (5/113), 53.09% (43/81) and 97.34% (220/226). Thus, it can be observed that the higher the ultrasound O-RADS classification, the higher the risk of malignancy. This was statistically significant. Taking O-RADS category 4 as the research objective, the patients were divided into two groups, pre-menopausal and post-menopausal for statistical analysis. Analysis revealed that the malignancy rate of postmenopausal O-RADS category 4 tumors was similar to that of O-RADS category 5. The risk of malignant tumors in postmenopausal women with O-RADS category 4 is significantly higher compared with that in premenopausal patients and the difference is statistically significant. The diagnostic efficacy of ROMA for benign and malignant tumors in postmenopausal patients was significantly greater when compared with premenopausal patients. When combined diagnosis is adopted, regardless of whether it is in the premenopausal or postmenopausal stage, the sensitivity and specificity of the diagnosis are significantly higher compared with those of a single diagnosis. Taking O-RADS category 4 as the research objective, the incidence of malignant tumors of O-RADS category 4 in postmenopausal women is similar to that of category 5. The diagnostic efficacy of ROMA for postmenopausal patients is greater when compared with that for premenopausal patients. The use of O-RADS classification combined with ROMA can improve the sensitivity and specificity for the differential diagnosis of benign and malignant ovarian-adnexal tumors.
Serum cancer antigen 125 (CA125) is the standard tool for surveillance of patients with epithelial ovarian carcinoma (OC). However, its utility may vary by histological subtype. The present study included patients with epithelial OC who completed primary therapy (surgery and chemotherapy) at the National Defense Medical College Hospital (Tokorozawa, Japan) between January 2006 and December 2022, achieved complete or partial response, and had a post-treatment CA125 level of <35 U/ml. Recurrence was defined using the Response Evaluation Criteria in Solid Tumors criteria via computed tomography (CT) imaging. Surveillance included quarterly CA125 testing for 5 years, and semiannual CT in year 1 followed by annual CT. All patients were classified into Group A, which included clear cell carcinoma and mucinous carcinoma, or Group B, which included high-grade serous carcinoma and other subtypes. Among 243 patients, there were 85 in Group A and 158 in Group B. First, the diagnostic performance of the standard CA125 cutoff (≥35 U/ml) for detecting recurrence was evaluated. The sensitivity was 28.6% in Group A and 81.8% in Group B; and the specificity was 98.4% in Group A and 98.8% in Group B. Second, because the sensitivity in Group A was very low, the CA125 ratio and a combined model (defined as CA125 ≥35 U/ml or CA125 ratio ≥1.5) were introduced. The CA125 ratio was defined as the maximum CA125 value measured at CT surveillance divided by the CA125 value measured just after the initial treatment for patients with CA125 <35 U/ml. The sensitivity was 66.7% in Group A and 93.5% in Group B; and the specificity was 84.1% in Group A and 86.4% in Group B. In conclusion, the utility of CA125 for the detection of recurrence differs substantially between histological subtypes, highlighting the need for histological subtype-specific surveillance strategies in epithelial OC.
