Search Results (164)

Background/Objectives: Tumor budding (TB)—clusters of one to five tumor cells at the invasive front—has emerged as a prognostic marker in various cancers. Its prognostic value in head and neck squamous cell carcinoma (HNSCC) is unclear. Methods: We retrospectively analyzed 98 HNSCC patients. The tumor buds were counted on hematoxylin–eosin-stained sections as per the 2016 International Tumor Budding Consensus Conference (ITBCC) guidelines. An optimal cutoff was determined by ROC analysis using excisional lymph nodes and five-year overall survival (OS) as the endpoint, stratifying patients into low- (≤4 buds) and high-risk (>4 buds) groups. The associations with clinicopathological features, OS, and disease-free survival (DFS) were assessed using Kaplan–Meier curves and Cox regression. Results: Among the 98 patients (median follow-up 58 months, range 18–108), 32 (32.7%) died. The optimal TB cutoff was 4.5 (AUC 0.85, 95% CI 0.76–0.93). High TB was associated with poorer five-year OS (26.4% vs. 85.3%). Multivariate Cox regression identified TB and extranodal extension as independent predictors of OS (TB HR: 3.4, 95% CI 1.3–9.2, p = 0.013). In the laryngeal cancer subgroup, TB was associated with worse survival in the univariate analysis (HR 7.5, 95% CI 1.6–35.6, p = 0.011), though this was not significant in the multivariate modeling. High TB independently predicted neck lymph node metastasis (multivariate OR 4.9, 95% CI 1.2–20.5, p = 0.029), which was present in 65.8% of the high-TB vs. 31.7% of the low-TB patients. High TB correlated with advanced AJCC stage and lymphovascular invasion. No clinicopathological factors, including TB, independently predicted DFS, in either the full cohort or the laryngeal subgroup. Conclusions: High tumor budding denotes an aggressive HNSCC phenotype and may guide decisions on elective neck dissection. Its assessment is simple, cost-effective, and potentially valuable for routine pathology, pending external validation. Full article

Histopathological grading of oral squamous cell carcinoma is currently based on differentiation of cells, while additional histological parameters, such as the tumor–stroma ratio (TSR), tumor budding (TB), or the combined TSR/tumor budding model could better assess tumor biological behavior and monitoring of patients. Background/Objectives: To integrate risk factors associated with tumor progression: the TSR, TB and TSR/tumor budding model, whose prognostic significance in oral cancer has not yet been evaluated. Methods: An observational cohort retrospective study assembled according to STROBE guidelines on histological materials from 196 patients with invasive squamous cell carcinoma of the oral cavity. The goal of the analysis was to evaluate the association between the tumor stroma ratio, tumor budding, and the combined model of TSR/TB with the clinical and pathologic features of patients with squamous cell carcinoma of the oral cavity and to determine the prognostic value of this model in relation to disease-free survival (DFS) Results: The analysis did not show that the tumor stroma ratio (TSR), tumor budding, and the combined model of TSR/tumor budding were statistically significantly associated with the occurrence of metastatic disease at the start of treatment or during postoperative follow-up, but confirmed the value of depth-of-invasion (DOI) as a negative prognostic factor (HR 15.3, p < 0.001). Conclusions: The TSR, TB, and the combined TSR/TB model were not found to be statistically significant predictors for the disease progression in the Cox regression survival analysis but were found to have a significant correlation with known negative prognostic factors: DOI, neural invasion, and T category. Full article

Gynecological malignancies (ovarian, endometrial, and cervical cancers), including disseminated intravascular coagulation (DIC), often provoke systemic coagulopathy. In recent years, tumor-derived, tissue factor–positive microparticles (TF⁺ MPs) have emerged as potent drivers of cancer-associated thrombosis and possibly DIC. These small (0.1–1 µm) membrane vesicles bud from cancer cell surfaces and carry procoagulant factors (phosphatidylserine and TF) on their surface. We review how TF⁺ MPs are generated by tumor cells and amplify the extrinsic coagulation cascade, potentially triggering DIC in patients with advanced gynecologic cancers. Clinical studies have linked el evated TF⁺ MP levels and activity to venous thromboembolism (VTE) in cancer, and small case series suggest dramatically high MP–TF activity in cancer-related DIC. We summarize evidence that TF⁺ MPs from ovarian tumors carry exceptionally high TF procoagulant activity (median ~80 pg/mL), and nearly all patients with cancer-associated VTE or DIC have MP–TF levels above normal. This review discusses diagnostic implications (e.g., measuring MP–TF activity as a biomarker) and treatment strategies (through the reduction in tumors, anticoagulation, and experimental TF inhibitors) in this setting. We also identify gaps in knowledge (standardized MP assays, prospective studies) and propose future directions (targeting MP formation or TF signaling). Two summary tables highlight recent studies of TF⁺ MPs in gynecologic cancer and their clinical outcomes. Illustrative figures depict the TF⁺ MP-triggered coagulation cascade and a conceptual framework for clinical management. Understanding TF⁺ MPs in gynecological cancer could improve the prediction and management of DIC and related thromboses. Full article

Background: The pancreas develops from two independent buds that fuse to form the adult organ. Ontogeny has largely been neglected in pancreatic surgery. This study aims to demonstrate that the adult pancreas can still be divided into morphogenetic units based on its embryological compartments and connective tissue borders for potential therapeutic purposes. Methods: Ten donor bodies (four female, six male, aged 73–101 years) were used. Manual dissection, guided by the common bile duct to locate the embryological fusion plane, was performed to divide the pancreatic tissue. Immunohistochemical staining for pancreatic polypeptide differentiated the pancreatic tissue by embryological origin and was used to quantify dissection accuracy. Results: Landmark-guided dissection successfully separated the pancreas along a connective tissue plane in seven cases. The resulting compartments were distinctly divided along the dissection plane into an area rich in pancreatic polypeptide and an area with low accumulation. Two cases showed deviations from the dissection plane at the histological level. One case contained tumor tissue, interfering with the utilization of landmarks. Conclusions: Landmark-guided dissection of the pancreas based on its embryological fusion plane allows for reliable separation into morphogenetic compartments. Immunohistochemical staining for pancreatic polypeptide effectively differentiates tissue origins. This approach may enable more precise, differentiated pancreatic resections and tailored treatments, with potential for refinement in routine surgical practice. Approaching the pancreatic tissue with regard to its ontogenetic origin and its clearly distinguishable compartments might even enable tailored treatment beyond refined surgical procedures. Full article

Background/Objectives: Several histopathological risk factors have been examined in vulvar cancer (VC) so far. However, the prognostic relevance of morphological biomarkers such as tumor budding (TB) and poorly defined clusters (PDCs) remains to be determined. Material and Methods: We histologically analyzed the formation of peritumoral and intratumoral TB and PDCs in a cohort of 157 patients with VC. We assessed their association with clinico-pathological features and evaluated their prognostic impact in terms of the risk of local recurrence and occurrence of metastasis (Fisher’s exact test) as well as overall survival (Log-rank test). Results: We determined a distinct prognostic relevance of peritumoral TB with regard to occurrence of metastasis (Fisher’s exact test; p = 0.0415) as well as a significant reduced risk of local recurrence in the group with absent intratumoral TB (Fisher’s exact test; p = 0.0004). Furthermore, we showed that patients without peritumoral budding formation had a significant superior prognosis in terms of overall survival (p = 0.0366, x² = 4.370). Conclusions: This study shows that several new histomorphological biomarkers may serve useful in predicting the clinical course of patients with VC, identifying patients at a lower risk of developing metastases/local recurrence as well as improved overall survival. Full article

Background: This study aimed to compare the clinical, pathological, and biochemical characteristics of upper rectal cancer (URC) and mid–lower rectal cancer (MLRC) in stage II and III non-metastatic rectal cancer and to identify distinct prognostic factors influencing survival and recurrence. Material and Methods: This retrospective cohort study included 100 patients with stage II and III non-metastatic rectal adenocarcinoma who underwent neoadjuvant chemoradiotherapy (nCRT) followed by curative-intent surgery between 2021 and 2024. Patients were categorized into URC (n = 53) and MLRC (n = 47) groups. Parameters analyzed included demographic factors, ASA score, surgical characteristics, pathological features (tumor stage, lymph node involvement, lymphovascular invasion (LVI), perineural invasion (PNI), tumor budding, tumor regression grade (TRG)), and biochemical markers (carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), white blood cell (WBC) count, neutrophil count, platelet count (PLT), and C-reactive protein (CRP)). One-year overall survival (OS) and disease-free survival (DFS) were analyzed using Kaplan–Meier survival curves, and Cox regression models identified independent prognostic factors. Results: Preoperative CEA levels were higher in MLRC (p = 0.05), whereas WBC count (p = 0.01), neutrophil count (p = 0.02), PLT (p = 0.01), and CRP levels (p = 0.01) were higher in URC. Pathological analysis revealed higher LVI (p = 0.04), PNI (p = 0.04), and tumor budding (p = 0.03) in MLRC. At one-year follow-up, OS rates were 82.1% (URC) vs. 80.3% (MLRC) (p = 0.85), and DFS rates were 78.6% (URC) vs. 73.4% (MLRC) (p = 0.72). Multivariate Cox regression analysis identified age (HR: 1.04, p = 0.03), ASA score (HR: 1.22, p = 0.01), CRP (HR: 1.18, p < 0.001), preoperative CEA (HR: 1.12, p = 0.02), preoperative CA19-9 (HR: 1.09, p = 0.03), LVI (HR: 1.42, p < 0.001), PNI (HR: 1.35, p = 0.02), and tumor budding (HR: 1.28, p = 0.03) as independent prognostic factors for OS. Similar trends were observed for DFS, with T stage (HR: 1.35, p = 0.01) and tumor size (HR: 1.22, p = 0.01) also being found significant. Conclusions: Inflammatory markers, tumor burden indicators (LVI, PNI, budding, tumor size, T stage), and preoperative CEA/CA19-9 were identified as significant predictors, suggesting a risk-adapted approach to rectal cancer treatment. Full article

Background/Objectives: Identifying tumor budding (TB) in colorectal cancer (CRC) is vital for better prognostic assessment as it may signify the initial stage of metastasis. Despite its importance, TB detection remains challenging due to subjectivity in manual evaluations. Identifying TBs remains difficult, especially at high magnification levels, leading to inconsistencies in prognosis. To address these issues, we propose an automated system for TB classification using deep learning. Methods: We trained a deep learning model to identify TBs through weakly supervised learning by aggregating positive and negative bags from the tumor invasive front. We assessed various foundation models for feature extraction and compared their performance. Attention heatmaps generated by attention-based multi-instance learning (ABMIL) were analyzed to verify alignment with TBs, providing insights into the interpretability of the features. The dataset includes 29 WSIs for training and 70 whole slide images (WSIs) for the hold-out test set. Results: In six-fold cross-validation, Phikon-v2 achieved the highest average AUC (0.984 ± 0.003), precision (0.876 ± 0.004), and recall (0.947 ± 0.009). Phikon-v2 again achieved the highest AUC (0.979) and precision (0.980) on the external hold-out test set. Moreover, its recall rate (0.910) was still higher than that of UNI’s (0.879). UNI exhibited a balanced performance on the hold-out test set, with an AUC of 0.960 and a precision of 0.968. CtransPath showed strong precision on the external hold-out test set (0.947) but had a slightly lower recall (0.911). Conclusions: The proposed technique enhances the accuracy of TB assessment, offering potential applications for CRC and other cancer types. Full article

Tumor budding (TB) occurs at the deepest site of tumor invasion and is a significant prognostic indicator of cervical metastasis in oral squamous cell carcinoma (OSCC). The mechanism of TB, however, remains unclear. This study investigated the roles of the tumor microenvironment and partial epithelial–mesenchymal transition (p-EMT) in TB expression using molecular and cellular physiological analyses. We established oral metachronous carcinoma cell lines (gingival carcinoma: 020, tongue carcinoma with high TB expression: 020G) from two cancers with pathologically different TB in the same patient and subjected them to exome analysis to detect gene mutations related to carcinogenesis and malignancy. Differences in EMT expression induced by transforming growth factor-β (TGF-β) between 020 and 020G were analyzed by Western blotting and reverse transcription polymerase chain reaction, and TGF-β-induced changes in cell morphology, proliferation, migration, and invasive ability were also examined. TGF-β expression was observed in the deepest tumor invasion microenvironment. TGF-β also induced the expression of several p-EMT markers and increased the migration and invasive abilities of 020G compared with 020 cells. In conclusion, TGF-β in the deep-tumor microenvironment can induce p-EMT in tumor cells, expressed as TB. Full article

Background: Cemento-ossifying fibroma (COF) is a benign, non-aggressive fibro-osseous tumor in which normal bone is replaced by fibrous tissue containing collagen fibers, bone, or cementum-like material. Although COF is rare in children, its occurrence requires careful management due to its potential impact on tooth development and occlusion. Surgical excision is the widely used treatment; however, post-operative occlusal guidance is crucial, particularly in pediatric patients. Case report: This case report presents the early intervention using a preformed eruption guidance appliance (EGA) following the excision of COF in a 5-year-old boy. The patient exhibited premature loss of the primary canine and displacement of the devel-oping permanent tooth bud. After surgical excision, an EGA was applied to facilitate proper eruption of the successor teeth and optimize oral muscle function. Over a four-year follow-up period, the permanent teeth in the affected area erupted favorably, and intercuspal relationships improved during the transition from primary to mixed dentition. Conclusions: Given the limited research on the long-term effects of COF on developing dentition, long-term follow-up and additional studies are necessary to further evaluate its impact and the effectiveness of eruption guidance appliances in pediatric patients. Full article

Background and Objectives: This study examined factors influencing the onset and progression of colorectal tumors, including patients’ epidemiological data, tumor location (right-sided, left-sided, and rectal), histomorphology, perineural or intraneural invasion, lymph node status, immune reactions, mismatch repair (MMR) status, and commonly observed mutations. Our primary goal was to evaluate their predictive and prognostic value and interactions. Materials and Methods: We analyzed a retrospective cohort of 100 patients with colorectal adenocarcinoma diagnosed between 2020 and 2023, using formalin-fixed paraffin-embedded (FFPE) tumor blocks. The methods included routine H&E microscopy, immunohistochemistry, Next-Generation Sequencing (NGS), and subsequent statistical analysis. Results: The findings showed a median diagnosis age of 70 years, with no gender-specific tumor localization. Right-sided tumors were prevalent, especially among patients with a defective MMR (dMMR), which represented 89% of dMMR cases. MMR status significantly correlated with tumor localization. We observed significant relationships between tumor grade, lymphovascular invasion, and overall tumor stage. Higher tumor grades and stages correlated with increased lymphovascular invasion and lymph node involvement. Interestingly, tumor budding did not correlate with lymph node metastasis but was significantly associated with higher tumor grades. Most BRAF mutations were found in right-sided tumors, indicating a significant correlation with this localization. Conclusions: This study focuses on the diversity of colorectal cancer (CRC) by examining how genetic and histological characteristics vary based on tumor location or other tumor variables. Full article

Background/Objectives: The aim of this study was to examine the expression of TYK2 in colorectal cancer (CRC) and to determine the potential diagnostic and prognostic significance of this kinase. Methods: Digital image analysis was performed to assess immunohistochemical TYK2 reactivity. Results: There were significant differences for all positive pixels between CRC and normal colonic mucosa, with higher TYK2 expression levels observed in surgical margins than in adenocarcinomas (p = 0.0004). Paired t tests showed elevated immunoreactivity for overall TYK2 expression in matched pairs of CRC with adjacent surgical margins (p < 0.0001). Higher percentages of weak (p < 0.0001) and strong pixels (p = 0.0260) were detected in normal colonic mucosa than in cancer tissues. To distinguish cancer from normal intestinal mucosa, the following cutoffs for the TYK2 immune score were found: 29.5% for all cases and 31% for matched pairs. Tumor budding (Bd) was negatively correlated with the percentage of strong pixels for TYK2 (ρ = −0.270, p = 0.0096). The percentage of strong pixels was significantly elevated for the T parameter (p = 0.0428). There was a positive correlation between the number of involved lymph nodes and weak pixels (ρ = 0.239, p = 0.0242). Immunofluorescence staining showed significantly higher signal intensities in colonic mucosa than in CRC. The protein level of TYK2 was significantly higher in controls than in cancer tissues. TEM imaging showed lower levels of TYK2 in cancer than in ulcerative colitis. Conclusions: TYK2 protein expression may bring diagnostic value in patients diagnosed with CRC. Full article

Staphylea bumalda is a rare medicine and edible shrub native to the temperate regions of Asia, possessing significant medicinal potential. In this study, the components of S. bumalda tender leaves and buds extract (SBE) were analyzed and identified by HPLC and LC/MS method, and the safety of SBE was evaluated through mouse acute toxicity models. The protective effects of SBE on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in mice were investigated in terms of inflammatory factor levels, oxidative stress, and gut microorganisms. Results showed that hyperoside, kaempferol-3-O-rutinoside, isorhoifolin, and rutin were the main components of the extract, and SBE demonstrated good safety in experimental mice. SBE could alleviate weight losing, disease activity index (DAI) raising, and colon shortening in mice. Pathological section results showed that the inflammatory cell infiltration decreased significantly, and the number of goblet cells increased significantly in the SBE group. After SBE treatment, interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) levels in serum were significantly decreased, and the levels of myeloperoxidase (MPO) and nitric oxide (NO) in colon tissues were significantly decreased. SBE inhibited gut inflammation by increasing Lactobacillus. In summary, SBE played a therapeutic role in UC mice by relieving colon injury, reducing inflammatory factor levels, and maintaining gut flora homeostasis. SBE is expected to become an auxiliary means to participate in the prevention and treatment of UC. Full article

Background/Objectives: Bladder cancer, predominantly urothelial carcinoma, is an important malignancy of the urinary system. Despite the same histologic grade and stage, some patients seem to have a worse prognosis. In this context, the epithelial–mesenchymal transition (EMT), characterized by the loss of E-cadherin and gain of vimentin expression, is an important process in tumor progression. Galectin-3, a lactose-binding protein involved in various cellular processes, has been associated with increased tumor cell migration, invasion, and treatment resistance. Methods: In this study, 223 bladder cancer cases were examined, and E-cadherin, vimentin, and galectin-3 expression was evaluated by immunohistochemical staining in tumor budding areas and invasive components. These markers were also correlated with clinicopathological parameters, including tumor grade and stage. Results: The results indicated a significant decrease in E-cadherin expression and an increase in vimentin staining in higher-grade and higher-stage tumors, supporting EMT involvement. Galectin-3 expression was notably higher in T1 high-grade tumors but decreased in T2 stage tumors. Despite this, no significant correlation was found between galectin-3 and E-cadherin or vimentin, suggesting a complex role of galectin-3 in EMT. Conclusions: High galectin-3 expression in T1 high-grade tumors highlights its potential role in early tumor progression and as a therapeutic target. However, the decrease in its expression in advanced stages underscores the need for further research to understand its multifaceted involvement in bladder cancer. These findings suggest that while galectin-3 may contribute to the EMT and early tumor progression, its exact role and potential as a therapeutic target require more detailed investigation. Full article

Background and Objectives: Squamous cell carcinoma (SQCC) represents a significant proportion of human malignancies affecting various anatomical sites, including the lung. Understanding the prognostic factors is crucial for establishing effective risk stratification in these patients, as multiple critical aspects significantly impact overall survival. Materials and Methods: A retrospective study was conducted on 99 patients with operable lung SQCC treated at a tertiary center. The exclusion criteria included patients under 18, those with in situ or metastatic SQCC, and those who received neoadjuvant therapy. The surgical specimens were re-analyzed, and data were collected on multiple variables, including pTNM staging, tumor characteristics, and overall survival (OS). The Kaplan–Meier survival analysis and Cox regression models were used to identify significant prognostic factors. Results: The Kaplan–Meier analysis showed a median survival of 36 months with a 65.65% mortality rate. Significant factors influencing survival included keratinization, histological grading, tumor size and stage, pleural invasion, tumor cell arrangement, tumor budding, spread through air space (STAS), and mitotic index. A multiple Cox regression highlighted the nonkeratinizing tumors, advanced pT stages, single-cell invasion, and high mitotic index as key predictors of poorer outcomes. The nonkeratinizing tumors showed higher mortality and shorter median survival rates compared to keratinizing tumors. The tumor staging, cell arrangement, and tumor budding significantly impacted the survival curves. Conclusions: The study underscores the importance of detailed histopathological evaluations in lung SQCC. The nonkeratinizing tumors, advanced pT stage, single-cell invasion, and high mitotic index were associated with higher hazard rates, emphasizing the need for a comprehensive grading system incorporating these factors to improve prognostic accuracy and guide treatment strategies. Full article