Search Results (315)

Background and Clinical Significance: Oropharyngeal squamous cell carcinoma (OPSCC) and small-cell neuroendocrine carcinoma (SCNEC) are biologically distinct entities with markedly different prognostic and therapeutic implications. While HPV-negative OPSCC carries worse outcomes than HPV-positive disease, SCNEC is exceedingly rare, highly aggressive, and prone to early systemic dissemination. Their synchronous occurrence in the head and neck (HN) is exceptional and poses major diagnostic and therapeutic challenges. Case Presentation: A 54-year-old male, smoker and alcohol consumer, presented with a left tonsillar lesion and cervical lymphadenopathy. Biopsy confirmed p16-negative OPSCC. He underwent transoral robotic surgery with modified radical neck dissection. Histopathology unexpectedly revealed two distinct malignancies: keratinizing OPSCC in the tonsil and high-grade SCNEC in a cervical lymph node, confirmed by immunohistochemistry (synaptophysin, CD56, Ki-67 80%). Postoperative FDG-PET/CT performed within two months showed rapid systemic spread, including paravertebral, pulmonary, and pelvic nodal metastases. Despite recommendation for systemic therapy, the patient deteriorated quickly and died shortly thereafter. Conclusions: This study reports coexistence of p16-negative OPSCC and high-grade SCNEC in the HN. It highlights the diagnostic complexity, staging limitations, and therapeutic dilemmas of discordant histologies, while illustrating the fulminant clinical course typical of SCNEC of unknown origin. Early recognition, comprehensive pathology, and multidisciplinary management are essential, although prognosis remains dominated by the aggressive neuroendocrine component. Full article

Computer-aided diagnostic technologies have demonstrated substantial advantages in 3D medical image segmentation, particularly in multimodal 3D medical image segmentation tasks, where they play a pivotal role in driving continuous innovation in related architectures. As an integration of U-Net and Transformer, the UNETR architecture has demonstrated remarkable efficacy in 3D medical image segmentation. Nevertheless, despite its successes, UNETR remains challenged by clinical complexities such as intricate tumor localization and anatomical structural diversity in complex clinical settings. To address these issues, we propose an enhanced 3D segmentation framework, UAtten-Unetr, designed to improve segmentation accuracy and robustness in complex medical scenarios. The framework captures global contextual information via hierarchical Transformer layers and incorporates a spatial–channel attention module to enable adaptive fusion of multimodal features, thereby effectively enhancing cross-modal feature alignment capabilities. Concurrently, we innovatively developed a unified loss function based on bimodal modality-specific Dice constraints and uncertainty regularization, optimized for synchronous learning across the ACDC (cardiac MRI) and AMOS22 (abdominal CT/MRI) datasets. Experimental results showed that UAtten-Unetr achieved an average Dice score of 92.20% on the ACDC dataset, exceeding the reported nnU-Net result of 91.61% by 0.59 percentage points. On the AMOS22 dataset, the proposed method achieved an average Dice score of 84.51%, exceeding the reported UNETR result of 78.33% by 6.18 percentage points. However, its myocardium Dice score (84.11%) was lower than those of nnU-Net (89.24%) and MT-UNet (89.04%), indicating a remaining limitation in myocardium boundary segmentation. These results indicate competitive segmentation performance under the reported experimental settings. This method delivers dual improvements in accuracy and generalization across complex anatomical scenarios, providing an effective solution for precise diagnosis in intricate clinical environments. Full article

Pancreatic ductal adenocarcinoma (PDAC) remains a highly lethal malignancy, highlighting the need for reproducible experimental systems that model pancreatic injury and subsequent neoplastic progression. Adult-onset genetically engineered models in which oncogenic Kras and mutant Trp53 are induced in the pancreas provide a relevant platform for studying PDAC pathogenesis, but efficient neoplastic progression often requires concomitant pancreatic injury. Cerulein-induced pancreatitis is widely used to provide an injury-associated inflammatory stimulus that promotes PDAC progression; however, repeated-injection regimens are labor-intensive and increase cumulative handling stress in animals. Here, we describe a dose-optimized, single-dose L-Lysine protocol designed to induce acute pancreatitis and characterize subsequent pancreatic neoplastic progression in adult-onset Kras/Trp53-driven mice. Tamoxifen-treated Ptf1a^CreER/+; Kras^LSL-G12D/+; Trp53^LSL-R172H/+; Rosa26-RFP mice received a single intraperitoneal injection of L-Lysine, followed by biochemical, histological, and immunohistochemical assessment of pancreatic injury and tumor development. A single 2.0 g/kg L-Lysine injection induced sublethal acute pancreatitis characterized by increased serum pancreatic enzymes, interstitial edema, inflammatory cell infiltration, acinar cell necrosis, and rapid mitochondrial alterations. During 3–6 months of follow-up, mice developed multifocal acinar-to-ductal metaplasia, PanIN lesions, invasive PDAC, and peritoneal dissemination. This protocol provides a simple, synchronized, and less labor-intensive model for studying pancreatic injury and subsequent neoplastic progression in adult-onset Kras/Trp53-driven mice. Full article

Background/Objectives: Hepatoid adenocarcinoma is a rare adenocarcinoma subtype. Synchronous esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcinoma with hepatoid differentiation is exceptionally uncommon. This report describes lesion-specific staging, pathological response assessment, and individualized management after neoadjuvant chemoimmunotherapy. Methods: De-identified clinical, imaging, laboratory, operative, and pathological data were retrospectively reviewed. Both lesions were staged according to the AJCC 8th edition and reassessed using the CAP modified Ryan four-tier tumor regression grading system. Results: A 61-year-old man presenting with dysphagia had separate ESCC and gastric cardia adenocarcinoma, both staged cT2N0M0. One cycle of pembrolizumab 200 mg, nab-paclitaxel 300 mg, and cisplatin 100 mg was administered. Agranulocytosis precluded further neoadjuvant therapy; after neutrophil recovery, R0 resection was performed. Pathological review showed ESCC ypT1aN0M0, score 1, and cardia adenocarcinoma ypT1aN0M0, score 3, with approximately 30% regional hepatoid differentiation. All 10 examined lymph nodes were negative. AFP was not measured before treatment; post-treatment/preoperative values were 14.45 and 14.68 ng/mL, and the postoperative value was 6.08 ng/mL. Postoperative tislelizumab monotherapy was selected as an individualized, non-standard strategy, mainly because of affordability. At approximately 6 months after surgery, no recurrence, metastasis, or maintenance-related adverse event was identified. Conclusions: This case emphasizes biopsy under-sampling and lesion-specific staging and pathological assessment. The regression-score difference is descriptive and confounded by baseline burden, histology, and one-cycle exposure; the AFP findings do not validate a surveillance biomarker. Full article

Background: The molecular changes associated with the progression of intraductal papillary mucinous neoplasm (IPMN) to pancreatic ductal adenocarcinoma (PDAC) and distant metastasis remain incompletely understood. Case Presentation: A man in his late 70s underwent pancreaticoduodenectomy and partial hepatectomy for a pancreatic head tumor with synchronous liver metastasis. Histology showed a 4.5 cm moderately differentiated PDAC arising in an IPMN with high-grade dysplasia (pT3N1M1). Genomic analysis of the IPMN, PDAC, and liver metastasis identified KRAS p.G12D, CDKN2A deletion, and GNAS p.R201H in the IPMN; additional SMAD4 p.R361C in the PDAC; and KRAS p.G12D, CDKN2A deletion, SMAD4 p.R361C, and APC p.R1450Ter in the liver metastasis. The APC alteration was confirmed by targeted sequencing and was accompanied by loss of heterozygosity at the APC locus. β-Catenin showed membranous expression in the IPMN and PDAC, but nuclear accumulation in the liver metastasis. Discussion: The shared KRAS, CDKN2A, and SMAD4 alterations support a common clonal origin of the PDAC and metastatic tumors. The absence of a detectable GNAS alteration in the liver metastasis and the presence of a metastasis-specific APC alteration are compatible with, but do not prove, branching evolution and selection of a metastatic subclone. Conclusions: This case shows a metastasis-specific heterozygous APC truncating alteration with loss of heterozygosity, accompanied by nuclear β-catenin accumulation, in an IPMN-associated PDAC. Full article

Background: The neutrophil-to-lymphocyte ratio (NLR) has been the focus of extensive research in recent years as an inexpensive inflammatory biomarker with prognostic value in oncology, but its relationship with tumor grade across solid malignancies remains uncertain. Methods: This systematic review evaluated original clinical studies reporting the association between peripheral blood NLR and histological tumor grade in solid tumors. PubMed and Web of Science were searched using Boolean strategies, and eligible full-text studies were synthesized qualitatively because of heterogeneity in tumor type, grading system, NLR threshold, and statistical reporting. Results: The qualitative synthesis included 13 retrospective primary studies comprising 5394 patients. Eight studies reported statistically significant associations between higher NLR and higher tumor grade or poorer differentiation, most consistently in bladder cancer and in single studies of prostate cancer, soft tissue sarcoma, renal cell carcinoma, pancreatic cancer, breast cancer, and colorectal cancer with synchronous liver metastases. Four studies reported no statistically significant grade-related association, mainly in heterogeneous breast cancer and ovarian cancer cohorts, whereas a small colorectal adenocarcinoma cohort study showed a non-significant positive trend. Conclusions: The available evidence suggests a possible relationship between systemic inflammation and tumor grade in selected malignancies, but the evidence remains preliminary, tumor-specific, retrospective, and vulnerable to confounding. NLR should not be interpreted as a surrogate for histological grade. Full article

Background: The Martini and Melamed criteria for diagnosing multiple primary lung cancers (MPLCs) have remained in use for half a century despite substantial changes in lung cancer epidemiology, risk factors, imaging technologies, and treatment approaches. Correspondingly, the landscape of MPLC has likely changed, necessitating revisions to their diagnostic guidelines. Research Question: What are the clinicopathologic profiles of modern-day MPLC patients, and can these features be used to identify a subset of patients classified as MPLC that may warrant additional investigation as intrapulmonary metastasis (IPM)? Study Design and Methods: We conducted a retrospective cohort study using electronic medical record data from patients who underwent multiple lung cancer resections at Mount Sinai Hospital. Patient demographics, tumor characteristics, and surgical treatments were compared with those reported in the original Martini and Melamed series. We then proposed a reclassification framework incorporating a CT-based assessment of synchronous versus metachronous tumors and contemporary clinicopathologic features documented in imaging and pathology reports. Results: Ninety-one patients underwent successive lung cancer resections. Among first nodules treated with surgical resection, 46% exhibited pathologic features suggestive of metastasis within the lung, including visceral pleural invasion (18%), vascular invasion (24%), lymphatic invasion (36%), and/or lymph node positivity (3%). In contrast, among second nodules (second temporal surgery), 45% demonstrated ground-glass opacity (GGO) supportive of a diagnosis of MPLC. Using the original criteria, 83 patients (91%) were classified as having MPLC; this proportion decreased to 53 patients (58%) under the reclassification criteria. Regardless of the criteria applied, contemporary MPLCs were more likely to occur in older patients, women, those with adenocarcinoma histology, and treated with sublobar resections compared with MPLCs described in the Martini and Melamed era. Conclusions: MPLCs are increasingly recognized, and their clinical presentation has changed substantially over time. Modern imaging and pathologic assessment may be useful tools for diagnosing MPLCs, but this requires future validation. This has important implications for staging and treatment decision-making, as patients may be undertreated by not being offered multimodal treatments or over-treated with systemic therapy when surgery alone may be sufficient. Full article

Synchronous low-grade alimentary lymphoma and gastrointestinal mast cell tumor have recently been described in cats. This report describes synchronous low-grade alimentary lymphoma and gastrointestinal mast cell tumor involving the jejunum in a cat. A 2.3 kg, 15-year-old, spayed female Chinchilla Persian cat presented with vomiting, diarrhea, anorexia, and lethargy. Ultrasonography and computed tomography demonstrated diffuse intestinal wall thickening and a focal jejunal lesion characterized by marked transmural thickening with loss of wall layering. Exploratory laparotomy and full-thickness intestinal biopsies were conducted. Histopathologic and immunohistochemical examination revealed two morphologically distinct neoplastic populations involving different jejunal wall layers. The two populations were anatomically adjacent but remained distinct without convincing intermingling in the examined histologic sections. These findings supported the interpretation of a lesion most consistent with a collision pattern. The affected intestinal segment was surgically resected, and chlorambucil and prednisolone were administered postoperatively. Clinical signs resolved, imaging abnormalities improved, and no evidence of local gastrointestinal mast cell tumor recurrence or progression of low-grade alimentary lymphoma was detected during the 14-month follow-up period. This case expands the currently recognized morphologic spectrum of synchronous feline intestinal neoplasia and highlights the importance of comprehensive histopathologic assessment and full-thickness intestinal biopsies for accurate diagnosis. Full article

Circadian rhythms synchronize physiological processes with the light–dark cycle and regulate biological functions relevant to cancer, including cell-cycle control, metabolism, DNA repair, immunity, and tissue homeostasis. Growing evidence indicates that disruption of these temporal mechanisms contributes to tumor initiation, progression, metastasis, and treatment response. In colorectal cancer (CRC), circadian clock dysregulation has emerged as an important component of tumor biology. A systematic search identified 1338 records, of which 43 studies met the eligibility criteria (20 human, 19 experimental, and 4 chronotherapy studies). Across the included studies, statistically significant associations were consistently reported between dysregulation of clock genes such as PER1, PER3, CLOCK, BMAL1, CRY1, TIMELESS, and ARNTL2 and alterations in proliferation, metabolism, epithelial plasticity, immune regulation, metastatic potential, and treatment responsiveness. Experimental evidence also supported interactions with Wnt signaling, ferroptosis, oxidative-stress adaptation, epithelial–mesenchymal remodeling, and a proposed clock–microbiota–immune axis. Overall, the available evidence indicates that circadian dysregulation represents a systems-level disturbance that gives rise to a multidimensional biological condition, here referred to as the Tumor Temporal State, integrating the metabolic, immune, invasive, and therapeutic dimensions of colorectal cancer biology. Full article

Background/Objectives: Intraoperative molecular imaging (IMI) enables real-time visualization of tumor biology during surgery using fluorescent probes and near-infrared imaging systems. As lung cancer screening increases detection of small and nonpalpable pulmonary nodules, conventional localization and margin assessment techniques remain limited, particularly during minimally invasive surgery. This review summarizes the technical foundations, imaging agents, clinical applications, and future directions of IMI in thoracic oncology. Methods: We performed a narrative review to synthesize current evidence regarding the technical foundations, molecular imaging agents, clinical applications, and future directions of intraoperative molecular imaging in thoracic oncology. Given the multidisciplinary scope of the field, a narrative approach was selected to integrate mechanistic, translational, and clinical evidence rather than to answer a single narrowly defined clinical question. Results: IMI generates dynamic intraoperative contrast based on preferential probe accumulation or activation within malignant tissue. Current approaches include non-specific fluorophores such as indocyanine green, activatable probes targeting tumor-associated proteases or acidic microenvironments, and receptor-targeted agents such as pafolacianine. Across prospective studies and multicenter trials, IMI improved localization of nonpalpable lesions, identified occult synchronous malignancies, and enhanced intraoperative margin assessment, frequently altering surgical management. Phase 2 and 3 studies of folate receptor-targeted imaging demonstrated clinically significant findings in a substantial proportion of patients, including lesions not detected by conventional imaging or palpation. However, performance remains dependent on tumor biology, target expression, lesion depth, and optical constraints. Conclusions: IMI represents an emerging transition from anatomy-guided toward biology-informed thoracic surgery by providing real-time molecular information during resection. Current evidence supports its role as a complementary intraoperative technology that augments conventional imaging and surgical techniques, particularly for small, peripheral, and nonpalpable lesions. Full article

Background: The survival benefit of primary tumor resection (PTR) in patients with synchronous metastatic primary malignant bone neoplasms (PMBNs) remains controversial. We aimed to evaluate the association between PTR and survival outcomes using a large population-based cohort with rigorous confounding control. Methods: Patients diagnosed with synchronous metastatic PMBNs (osteosarcoma, chondrosarcoma, Ewing sarcoma, and chordoma) between 2004 and 2022 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Patients were stratified by receipt of PTR. Propensity score matching (PSM; 1:1 nearest-neighbor, caliper = 0.03) was applied to balance baseline covariates. Kaplan–Meier analysis with log-rank testing and multivariable Cox proportional hazards regression stratified by matched pairs were used to assess overall survival (OS) and cancer-specific survival (CSS). Subgroup analyses were performed across four histological subtypes. Results: A total of 1046 patients were included (resection: n = 658, 62.9%; no resection: n = 388, 37.1%). After PSM, 488 patients (244 per group) were retained. In the matched cohort, PTR was independently associated with significantly improved Overall survival (OS) (HR = 0.34, 95% CI: 0.21–0.54, p < 0.001) and cancer-specific survival (CSS) (HR = 0.35, 95% CI: 0.22–0.55, p < 0.001). Subgroup analyses demonstrated significant survival benefit in osteosarcoma and chondrosarcoma (both p < 0.001), but not in Ewing sarcoma or chordoma. Conclusions: PTR is associated with a significant survival benefit in selected patients with synchronous metastatic PMBNs, particularly those with osteosarcoma and chondrosarcoma. These findings support individualized, multidisciplinary decision-making regarding surgical intervention in this population. Full article

Background/Objectives: Curcumin shows broad anticancer activity but limited clinical success as a standalone agent because of poor bioavailability and inconsistent tumor exposure. This review introduces the concept of curcumin as a molecular synergy amplifier and proposes that successful combinations depend on three interdependent determinants: mechanistic complementarity, suppression of adaptive resistance networks, and pharmacokinetic synchronization. Methods: Evidence on combinations with chemotherapeutics, natural bioactives, and nanotechnology-enabled delivery systems was critically evaluated, with emphasis on mechanism, resistance reversal, drug ratio, administration sequence, and tumor exposure. Results: Curcumin enhances therapeutic efficacy by sensitizing cancer cells, suppressing adaptive resistance pathways, targeting cancer stemness, and promoting multiple forms of programmed cell death. Importantly, analysis of current evidence indicates that therapeutic success depends not only on molecular synergy but also on pharmacokinetic synchronization between curcumin and partner agents. Many combinations demonstrating strong in vitro synergy fail to translate in vivo because optimal drug ratios, timing, and tumor exposure cannot be maintained. Nanotechnology-based co-delivery systems partially overcome these limitations through synchronized delivery and controlled release. Conclusions: Curcumin should be viewed as a molecular synergy amplifier whose clinical utility depends on mechanistic complementarity and pharmacokinetic synchronization with co-administered therapies. This framework provides a rationale for the design of next-generation curcumin-based combination therapies and identifies key priorities for clinical translation. Full article

Background: Reliable prognostic stratification is essential in metastatic colorectal cancer (mCRC), yet current inflammation-based scores do not fully integrate systemic inflammation, tumor burden, and clinical characteristics. Objective: This study aimed to develop a novel prognostic score integrating clinical, tumor burden, and inflammatory parameters in patients with mCRC and to compare its performance with the Glasgow Prognostic Score (GPS) and Gustave Roussy Immune Score (GRIm). Materials and Methods: This retrospective single-center study included 310 patients with mCRC treated between 2015 and 2025. GPS and GRIm were calculated. The novel prognostic score was constructed using seven equally weighted prognostic variables encompassing clinical characteristics, tumor burden, and laboratory parameters. Survival analyses were performed using Kaplan–Meier and Cox regression. Model performance was assessed using AUC, reclassification, calibration, and decision curve analysis. Results: Most patients had ECOG PS 0–1 (96.1%), left-sided tumors (76.1%) and synchronous metastases (79.0%). The median follow-up was 23.6 months. Both GPS and GRIm were independent prognostic factors for OS. GPS demonstrated superior discriminative performance compared with GRIm (AUC for 24-month OS: 0.697 vs. 0.620; p = 0.005). The novel score stratified median OS into low-, intermediate-, and high-risk groups as 40.9, 25.4, and 11.5 months, respectively (p < 0.001). The novel model outperformed GPS and GRIm (AUC: 0.768) and improved reclassification. Bootstrap-based internal validation demonstrated low optimism and good calibration. Conclusions: The novel prognostic score integrating clinical, inflammatory, and tumor burden parameters demonstrated superior prognostic performance compared with GPS and GRIm in mCRC. This score may serve as tool for individualized risk stratification. Full article

Background/Objectives: Virtual Bronchoscopic Navigation is used to guide bronchoscopes toward peripheral pulmonary lesions, but broad clinical and research adoption remains limited by the cost of proprietary software and by segmentation failures in small distal airways that can interrupt path planning. This study presents Virtual Bronchoscopic Pathfinder, an open-source, web-based system designed to provide automated airway segmentation, robust path generation, and browser-based three-dimensional visualization. Methods: The system integrates five components: a connectivity-aware deep learning model for pulmonary airway segmentation using Connectivity-Aware Surrogate and Local-Sensitive Distance modules; TotalSegmentator for automated tumor localization; a topology-preserving three-dimensional thinning algorithm implemented in C++ for centerline extraction; a bidirectional Dijkstra algorithm operating on a three-tier anatomical cost field with centerline, airway lumen, and parenchymal costs; and a zero-footprint visualization interface built on vtk.js with synchronized axial viewing and interactive volume rendering. VBP was validated on 306 thin-section CT series from 154 subjects in the public Lung-PET-CT-Dx dataset. Results: Among the 306 CT series, 33 series (10.8%) were excluded because of scanner-specific segmentation artifacts. In the remaining 273 anatomically valid series, the system successfully generated complete end-to-end navigation paths for all cases. The overall pipeline success rate was therefore 273 of 306 series (89.2%). The web-based interface was also confirmed to operate without client-side installation across desktop, laptop, and mobile device configurations. Conclusions: Virtual Bronchoscopic Pathfinder demonstrates that a reliable and accessible virtual bronchoscopic navigation workflow can be constructed entirely from open-source components. By combining connectivity-aware segmentation, cost-field path planning, and browser-based visualization, the system provides a practical foundation for imaging informatics research and future development of intra-procedural bronchoscopic guidance. Full article

Background: Soft tissue sarcomas (STS) are clinically heterogeneous, yet local recurrence (LR) and metastasis are typically analyzed as separate endpoints. We aimed to determine whether recurrence in STS is better understood as distinct phenotypes defined by the interaction between local and metastatic disease. Methods: A total of 668 patients with histologically confirmed STS from two tertiary sarcoma centers were analyzed using prospective registry data (2018–2025). Patients were stratified into four predefined recurrence phenotypes: no event, metastasis only, LR only, and combined LR and metastasis. Tumor characteristics, treatment variables, surgical factors, recurrence timing, and event sequence were analyzed across groups. Results: Phenotypes were distributed as follows: no event (52.2%), metastasis only (23.8%), LR only (13.5%), and combined recurrence (10.5%). High-grade tumors (G3) were more frequent in metastasis-only (73.0%) and combined phenotypes (65.7%) than in LR only (38.9%) and no event (28.9%) (p < 0.001). Early LR (≤365 days) occurred substantially more often in the combined phenotype (51.4%) than in isolated LR (17.8%), whereas late LR predominated in isolated cases (82.2% vs. 48.6%) (p < 0.001). Among patients with LR, high grade (OR 2.79, 95% CI 1.42–5.49) and axial location (OR 2.28, 95% CI 1.17–4.47) were independently associated with combined recurrence. In the combined phenotype, metastasis preceded LR in 40.0%, LR preceded metastasis in 34.3%, and events were synchronous in 25.7%. Conclusions: Recurrence in STS comprises distinct phenotypes defined by the interaction of local and metastatic disease. In particular, the clinical significance of local recurrence depends on its metastatic context. Full article