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Search Results (1,558)

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16 pages, 681 KB  
Article
Pathological Tumour Volume Percentage as a Quantitative Biomarker of Biological Aggressiveness in High-Risk Prostate Cancer
by Lorand Tibor Reman, Călin Chibelean, Daniel Porav-Hodade, Árpád-Olivér Vida, Ciprian Todea Moga, Veronica Maria Ghirca, Raul-Dumitru Gherasim, Rares-Florin Vascul, Orsolya-Brigitta Katona, Szabolcs Andre, Edva Anna Frunda and Orsolya Katalin Ilona Martha
Cancers 2026, 18(7), 1069; https://doi.org/10.3390/cancers18071069 (registering DOI) - 25 Mar 2026
Abstract
Background: Tumour volume percentage (TVP) is considered an important pathological parameter, particularly in prostate cancer, representing the ratio of tumour volume to the total gland, and it can be used to measure the quantity of malignancy. Previous reports have already demonstrated that [...] Read more.
Background: Tumour volume percentage (TVP) is considered an important pathological parameter, particularly in prostate cancer, representing the ratio of tumour volume to the total gland, and it can be used to measure the quantity of malignancy. Previous reports have already demonstrated that an elevated tumour volume percentage is associated with unfavourable factors, including extraprostatic extension, positive surgical margins, and lymph node metastasis. The independent value of TVP, especially in high-risk prostate cancer treated by radical prostatectomy, remains an area of active research, despite established prognostic factors such as PSA, ISUP grade, and TNM stage. Materials and Methods: We retrospectively analyzed the records of 159 high-risk prostate cancer patients who underwent open or laparoscopic radical prostatectomy between January 2016 and January 2025 at the Clinic of Urology of Targu Mures. High-risk patients were defined as those with ISUP grade 4–5 or PSA >20 ng/mL or clinical stage ≥T2c or stage cT3–4 and/or lymph node metastasis. Tumour volume percentage was calculated from the final pathology result and was determined as the proportion of prostate cancer volume relative to the total prostate volume. Clinical and pathological features, including PSA, ISUP grade, TNM stage, surgical margin, and lymph node involvement, were reported. To assess TVP as an indicator of tumour aggressiveness, univariate and multivariate regression analyses were performed. A p-value < 0.05 was considered statistically significant. Results: A total of 159 high-risk prostate cancer patients (100%), with a median age of 66 years, who underwent open or laparoscopic radical prostatectomy were included. The median tumour volume percentage was 7.6%, and the median prostate volume was 43.8 cc. On univariate analysis, patients with extraprostatic extension (p < 0.001), positive surgical margins (p = 0.005), a higher ISUP grade (p < 0.001), and lymph node metastasis (p = 0.006) exhibited higher TVP compared to their counterparts. A significant correlation was also observed between TVP and the number of positive biopsy cores (p < 0.001), a higher PSA value (p = 0.005), and a younger age (p = 0.041). Conversely, no correlation was identified between TVP and perioperative factors such as hospital stay, surgery duration, ICU days, type of approach, or positive urine culture. Two regression models on multivariate analyses were performed with TVP as the dependent variable. In the continuous variable model (Adjusted R2 = 0.43, p < 0.001), independent predictors of higher TVP were the number of positive biopsy cores (B = 0.54, p < 0.001), the number of positive lymph nodes (B = 2.59, p < 0.001), and surgical margin dimension (B = 1.19, p < 0.001). Age, PSA, and perioperative variables showed no significant correlation with TVP on multivariate analysis. In the categorical regression model (Adjusted R2 = 0.438), statistical significance was confirmed (F-test, p < 0.001). Independent predictors of increased tumour volume percentage included ISUP grade 5 in the effect-coded model (B = +6.60, 95% CI: 0.96–12.25, p = 0.022), and pathological TNM stage pT4 (B = +24.70, 95% CI: 17.69–31.70, p < 0.001). ROC analysis showed limited-to-moderate discrimination for positive surgical margins (AUC = 0.655; 95% CI 0.565–0.744; p = 0.001) and stronger discrimination for pN1 (AUC = 0.793; 95% CI 0.650–0.936; p = 0.002). The Youden-derived cut-offs were 4.90% for positive surgical margins and 5.77% for lymph-node metastasis. Conclusions: Tumour volume percentage is significantly associated with several adverse pathological features in high-risk prostate cancer. Rather than a standalone biomarker, its association with adverse pathological features underscores its potential role in risk stratification models, and the incorporation into pathology reports and prognostic nomograms may improve clinical decision-making. Full article
(This article belongs to the Section Cancer Biomarkers)
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10 pages, 543 KB  
Article
Prophylactic Supraclavicular Lymphadenectomy Does Not Improve Prognosis in Upper and Middle Thoracic Esophageal Squamous Cell Carcinoma: A Retrospective Single-Center Study
by Tomotake Ariyoshi, Koji Otsuka, Masahiro Kohmoto, Akira Saito, Kentaro Motegi, Takeshi Yamashita, Satoru Goto, Masahiko Murakami and Takeshi Aoki
Medicina 2026, 62(4), 625; https://doi.org/10.3390/medicina62040625 (registering DOI) - 25 Mar 2026
Abstract
Background and Objectives: The benefits of prophylactic supraclavicular lymph node dissection for esophageal squamous cell carcinoma (ESCC) remain controversial. This study investigated whether prophylactic supraclavicular (cervical) lymphadenectomy improves the long-term outcomes of patients with upper or middle thoracic esophageal squamous cell carcinoma. [...] Read more.
Background and Objectives: The benefits of prophylactic supraclavicular lymph node dissection for esophageal squamous cell carcinoma (ESCC) remain controversial. This study investigated whether prophylactic supraclavicular (cervical) lymphadenectomy improves the long-term outcomes of patients with upper or middle thoracic esophageal squamous cell carcinoma. Materials and Methods: This retrospective, single-center study included 290 patients who underwent thoracoscopic esophagectomy between January 2010 and December 2017. Patients treated with two-field lymphadenectomy (2FL) were compared with those who underwent prophylactic three-field lymphadenectomy (p3FL) after propensity score matching based on age, tumor location, clinical T and N stage, and preoperative treatment. The primary outcome was overall survival (OS), and secondary outcomes included postoperative complications and recurrence patterns. In a secondary analysis, the long-term outcomes were assessed in patients with solitary postoperative cervical (supraclavicular) lymph node recurrence in the 2FL group. Results: In the overall cohort, statistically significant differences were observed between the groups with respect to age, tumor location (p = 0.0002), cT and cN stages (p < 0.0001 and p < 0.0001), preoperative treatment (p = 0.02). No significant differences were observed between groups regarding age, organ for reconstruction, or postoperative complications. After propensity score matching, no significant differences were observed between the 2FL and p3FL groups in terms of overall survival or postoperative complications. Six patients (4.4%) in the p3FL group had pathologically confirmed supraclavicular lymph node metastasis, whereas four patients (2.6%) in the 2FL group developed solitary postoperative cervical lymph node recurrence. Patients with isolated cervical recurrence achieved favorable long-term survival following additional treatment. Conclusions: Prophylactic cervical lymphadenectomy did not improve the survival of patients with upper or middle thoracic esophageal squamous cell carcinoma. Given the low incidence of isolated cervical lymph node recurrence and the favorable outcomes achievable with additional treatment, routine prophylactic supraclavicular dissection appears unnecessary when two-field lymphadenectomy is feasible. Full article
(This article belongs to the Section Oncology)
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20 pages, 1364 KB  
Article
Basosquamous Cell Carcinoma: A Summary of the Definitions and Demographic, Clinical, Therapeutic, Histological, and Outcome Analysis of 20 Consecutive Basosquamous Cell Carcinomas in Comparison with 130 Basal Cell and 81 Squamous Cell Carcinomas in a Single Institution
by En Hyung Kim, Chang Gok Woo and Eui-Tae Lee
J. Clin. Med. 2026, 15(6), 2449; https://doi.org/10.3390/jcm15062449 - 23 Mar 2026
Viewed by 44
Abstract
Objectives: To clarify the characteristics of Basosquamous cell carcinoma (BSC), this study compares demographic, clinical, therapeutic, histological, and outcome findings of BSCs with those of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Methods: The authors classified various definitions of [...] Read more.
Objectives: To clarify the characteristics of Basosquamous cell carcinoma (BSC), this study compares demographic, clinical, therapeutic, histological, and outcome findings of BSCs with those of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Methods: The authors classified various definitions of BSC into three groups: the broadest, modest, and narrowest definitions. This study adopted the narrowest definition (both BCC and SCC features with transition zones in between) due to its wide use, its adoption by the World Health Organization, and the least heterogeneous definition. From 2009 to 2018, 20 consecutive cases of BSC presented in a single institution, along with 130 cases of BCC and 81 cases of SCC. Results: The statistically different parameters of BSC compared to BCC or SCC were age (SCC > BSC, BCC), duration (BSC, BCC > SCC), unclear border (BSC > BCC, SCC), higher NCCN classification (BSC, SCC > BCC), safety margin (SCC > BSC > BCC), operation time (BSC, SCC > BCC), reconstruction (less primary closure in BSC than BCC), microscopic size (BSC, SCC > BCC), perineural invasion (BSC > BCC), free lateral margin (BSC, SCC > BCC), and follow-up period (BSC > BCC, SCC). Regarding outcome, one distant metastasis (6.3%) in BSCs, no aggressive consequences in BCCs, and four local recurrences (11.1%), two lymph node metastases (5.6%), and one distant metastasis (2.7%) in SCCs were observed. Conclusions: In this Asian cohort, BSC has a trend toward higher rates of overall adverse outcomes compared to BCC, although this difference did not reach definitive statistical significance, unlike the findings reported in Caucasian populations. Early detection and appropriate treatment at the individual patient level are warranted to minimize rare but clinically relevant adverse events and reproduce favorable outcomes at the population level. Wide local excision followed by local flaps could be a successful surgical option with an adequate safety margin and double histopathologic intraoperative and postoperative check-up. Full article
(This article belongs to the Special Issue Skin Cancers: Update on Clinical Treatment and Management)
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28 pages, 755 KB  
Article
Exploratory Statistical Analyses of Clinical and Biochemical Factors for Differentiated Thyroid Cancer from a Romanian Cohort
by Alexandru Dima, Irina-Oana Lixandru-Petre, Denis Iorga, Gratiela Gradisteanu Pircalabioru, Dana Cristina Terzea, Andrei Goldstein, Florina Silvia Iliescu, Mihai Dascalu, Madalina Musat and Ciprian Iliescu
Cancers 2026, 18(6), 1036; https://doi.org/10.3390/cancers18061036 - 23 Mar 2026
Viewed by 87
Abstract
Background/Objectives: Thyroid cancer (TC) is among the most common endocrine malignancies, with incidence rates increasing worldwide. However, careful inferential analysis based on refined data is needed to provide a sharper clinical and epidemiological description of this serious condition in a biologically and technologically [...] Read more.
Background/Objectives: Thyroid cancer (TC) is among the most common endocrine malignancies, with incidence rates increasing worldwide. However, careful inferential analysis based on refined data is needed to provide a sharper clinical and epidemiological description of this serious condition in a biologically and technologically evolving society. This study presents an exploratory statistical analysis of data from 1470 patients who underwent thyroid surgery for differentiated TC. Methods: The analysis combines bivariate exploration of associations between variables with univariate and multivariate analyses stratified by histological subtype. We examined pathological characteristics (tumor location, nodal metastases, distant metastases, margin involvement, lymphovascular invasion, vascular invasion, and perineural invasion), clinical characteristics (clinical stage), biochemical markers (thyroglobulin, anti-thyroglobulin antibodies, and thyroid-stimulating hormone), and demographic variables (sex assigned at birth and age). In addition, exploratory multivariable models were used to investigate factors associated with lymph node metastasis and margin involvement in papillary microcarcinoma, the diffuse sclerosing variant, and the classical variant of papillary thyroid carcinoma. Results: Notably, moderate to high effect size correlations highlight the interdependence of invasive histopathological features in thyroid cancer and their collective link to adverse surgical outcomes and prognosis. Conclusions: This study provides an analysis of associations between the variables and subtype-specific descriptive estimates, serving as a foundation for future work in tailoring personalized medicine. Full article
(This article belongs to the Special Issue Advances in Cancer Data and Statistics: 2nd Edition)
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13 pages, 1634 KB  
Article
Alterations in PD-L1+ Myeloid Cells and Immune Infiltration Are Associated with Atezolizumab and Paclitaxel Therapy Success in a Triple-Negative Breast Cancer Model
by Kerim Bora Yilmaz, Ece Tavukcuoglu, Hamdullah Yanik, Pelin Seçken, Ertugrul Celik, Sumeyra Guler, Mehmet Mert Hidiroglu, Ibrahim Burak Bahcecioglu, Ismail Erturk, Mehmet Ali Gulcelik, Derya Karakoc and Gunes Esendagli
Medicina 2026, 62(3), 600; https://doi.org/10.3390/medicina62030600 - 22 Mar 2026
Viewed by 93
Abstract
Background and Objectives: A combination of chemotherapy and immunotherapy may improve cancer treatment outcomes; however, determining which patient groups will benefit from immunotherapy is critical. Triple-negative breast cancer (TNBC) achieves limited benefit from immune checkpoint inhibitors (ICIs) and anti-PD-L1 blockade therapy. Materials and [...] Read more.
Background and Objectives: A combination of chemotherapy and immunotherapy may improve cancer treatment outcomes; however, determining which patient groups will benefit from immunotherapy is critical. Triple-negative breast cancer (TNBC) achieves limited benefit from immune checkpoint inhibitors (ICIs) and anti-PD-L1 blockade therapy. Materials and Methods: In this study, PD-L1 expression levels in myeloid-derived cells in the tumor microenvironment were determined in an experimental TNBC model. Results: Compared with tumor cells, granulocytes, monocytes, and macrophages had significantly higher PD-L1 expression. CD206+ tumor-associated macrophages (TAMs) expressed the highest level of PD-L1. PD-L1 positivity in TAMs was also significantly high in the lung, liver, lymph node, and spleen. Despite treatment initiation in late-stage tumorigenesis, the combination of paclitaxel and the anti-PD-L1 monoclonal antibody atezolizumab significantly reduced tumor growth. In addition, lung metastasis burden was reduced with combined treatment compared with chemotherapy or anti-PD-L1 monotherapy alone. Conclusions: As a result, alterations in PD-L1+ myeloid cells and immune infiltration can be associated with atezolizumab and paclitaxel therapy success in triple-negative breast cancer. Full article
(This article belongs to the Special Issue Future Trends in Breast Cancer Management)
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12 pages, 1624 KB  
Article
Association Between Serum Vitamin D Levels and Colorectal Carcinoma: Insights from a Case Control Study in Northern Saudi Arabia
by Anass M. Abbas, Ashok Kumar Sah, Reef A. Alodhayd, Shahad A. Alblehed, Aryaf M. Almaeen, Saja T. Almadhor, Hala E. Sabaa, Rania Z. Alghafil, Nasir A. Nour, Abdulkhakov Ikhtiyor Umarovich, Ranjay Kumar Choudhary, Rabab H. Elshaikh and Manar G. Shalabi
Life 2026, 16(3), 512; https://doi.org/10.3390/life16030512 - 20 Mar 2026
Viewed by 302
Abstract
Background: Colorectal cancer (CRC) is a major global health concern and a leading cause of cancer-related mortality. In Saudi Arabia, it is the most common cancer among men and the third most common among women. The disease affects predominantly older adults, with an [...] Read more.
Background: Colorectal cancer (CRC) is a major global health concern and a leading cause of cancer-related mortality. In Saudi Arabia, it is the most common cancer among men and the third most common among women. The disease affects predominantly older adults, with an increasing number of cases reported in younger populations. Emerging evidence suggests a potential association between Vitamin D deficiency and CRC risk and progression. Aim: This study aimed to investigate the relationship between serum Vitamin D levels and colorectal cancer, and to evaluate its association with clinicopathological characteristics. Methodology: A retrospective case–control study was conducted on newly diagnosed CRC patients between January 2021 and August 2024 at King Abdul-Aziz Specialist Hospital, Prince Muteb Hospital, and the Oncology Center in Al Jouf, Saudi Arabia. A total of 100 CRC cases and 50 healthy controls were included. Serum 25-hydroxyvitamin D levels were measured and categorized as deficient (<20 ng/mL), insufficient (21–29 ng/mL), and normal (≥30 ng/mL). Histopathological features and tumor characteristics were analyzed. Statistical analyses included independent t-test, one-way ANOVA, and chi-square tests. Results: During the four-year period, 5399 gastrointestinal specimens were analyzed, of which 2111 (39.1%) were colorectal specimens. CRC was diagnosed in 107 cases (5.1%), and 100 patients met the inclusion criteria. The mean age of patients was 53.07 ± 13.3 years, and 69% were older than 50 years. Males represented 58% of cases (male-to-female ratio 1.4:1). Invasive adenocarcinoma was the predominant histological subtype (81%), with the sigmoid colon being the most common tumor site (39%). Vitamin D deficiency was significantly more prevalent in CRC patients (59%) compared to controls (22%). The mean serum Vitamin D level was significantly lower in cases (18.7 ± 11.3 ng/mL) than in controls (34.9 ± 15.6 ng/mL) (p < 0.001). No significant difference in Vitamin D levels was observed between males and females. Lower Vitamin D levels were significantly associated with advanced tumor grade (p = 0.004), lymphovascular invasion (p < 0.001), lymph node involvement (p = 0.001), and distant metastasis (p < 0.001). Representative histopathological images confirmed invasive moderately differentiated adenocarcinoma with characteristic malignant glandular architecture. Conclusions: Vitamin D deficiency was highly prevalent among colorectal cancer patients and was significantly associated with advanced tumor characteristics, including higher grade and metastatic features. These findings suggest a strong inverse relationship between serum Vitamin D levels and CRC development and progression. Further large-scale prospective and interventional studies are warranted to clarify the causal role of Vitamin D and its potential therapeutic implications in colorectal cancer prevention and management. Full article
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13 pages, 504 KB  
Article
Independent Risk Factors and a New Nomogram for Predicting Breast Cancer Risk for Bone Metastasis in Chinese Women: A Retrospective Study with External Validation
by Yunfei Huang, Tianjiao Ge, Heng Song, Wenjia Zhang, Meiqi Wang and Zhenchuan Song
J. Clin. Med. 2026, 15(6), 2324; https://doi.org/10.3390/jcm15062324 - 18 Mar 2026
Viewed by 128
Abstract
Background/Objectives: Bone is the most common organ affected by distant metastasis in advanced breast cancer, and the development of skeletal-related events (SREs) often leads to significant deterioration in patients’ quality of life and survival outcomes. In this study, we aimed to explore the [...] Read more.
Background/Objectives: Bone is the most common organ affected by distant metastasis in advanced breast cancer, and the development of skeletal-related events (SREs) often leads to significant deterioration in patients’ quality of life and survival outcomes. In this study, we aimed to explore the risk factors associated with bone metastasis in breast cancer and to develop a predictive nomogram for identifying high-risk patients, which may facilitate timely preventive interventions and improve clinical prognosis. Methods: A retrospective analysis was conducted on 672 patients with breast cancer who underwent surgery at the Fourth Hospital of Hebei Medical University (Shijiazhuang, China) between 2013 and 2023; this cohort served as the training set. Clinical and pathological characteristics potentially influencing bone metastasis—including age, menopausal status, histological grade, affected side, maximum tumor diameter, lymph node staging, TNM staging, ER status, PR status, HER-2 status, Ki-67, molecular subtypes, vascular tumor thrombus, nerve infiltration and visceral metastasis—were collected. The median follow-up time was 42 months. Patients were stratified into two cohorts based on whether postoperative bone metastasis occurred, with groups matched according to Tumor–Node–Metastasis (TNM) stage. Univariate and multivariate logistic regression models were applied to identify independent factors associated with breast cancer bone metastasis, and a nomogram prediction model was constructed using the variables retained in the final analysis. For external validation, data from 2814 patients with breast cancer who underwent surgery between 2013 and 2021 were extracted from the U.S. Surveillance, Epidemiology, and End Results database. Results: The multivariate logistic regression analysis revealed that histological grade (p = 0.002), progesterone receptor (PR) negativity (p = 0.001), human epidermal growth factor receptor 2 (HER-2) negativity (p = 0.002) and visceral metastasis (p < 0.001) were identified as independent predictors of bone metastasis in breast cancer. A nomogram predictive model was established using these four factors. The area under the receiver operating characteristic curve was 0.720 (95% confidence interval (CI): 0.6797–0.7607) for the training cohort and 0.701 (95% CI: 0.6813–0.7205) for the external validation cohort. Decision curve analysis further confirmed the clinical applicability of the model. Conclusions: The present study confirms that histological grade, PR status, HER-2 status and visceral metastasis are independent factors associated with bone metastasis in breast cancer. The constructed nomogram may effectively predict breast cancer-related bone metastasis and could serve as a practical tool for clinical decision-making. Full article
(This article belongs to the Special Issue Breast Cancer: Advances in Clinical and Personalized Practices)
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14 pages, 3795 KB  
Article
FOXP3+ Cells in Tertiary Lymphoid Structures Have Adverse Impact on Overall Survival in Patients with Gastric Cancer
by Ana Paparella Karaman, Tomislav Ivanović, Krešimir Mustapić, Katarina Vukojević, Luka Minarik, Merica Glavina Durdov and Petar Đolonga
Med. Sci. 2026, 14(1), 145; https://doi.org/10.3390/medsci14010145 - 18 Mar 2026
Viewed by 141
Abstract
Background/Objectives: Patients with local/locally advanced gastric cancer (GC) undergo gastrectomy/lymphadenectomy, but recurrences are common and the disease usually progresses to death. Tertiary lymphoid structures (TLS) of varying maturity can be observed in the immune microenvironment of the primary tumor. The aim of [...] Read more.
Background/Objectives: Patients with local/locally advanced gastric cancer (GC) undergo gastrectomy/lymphadenectomy, but recurrences are common and the disease usually progresses to death. Tertiary lymphoid structures (TLS) of varying maturity can be observed in the immune microenvironment of the primary tumor. The aim of the study was to analyze the association of TLSs and their immune cellular composition with clinicopathological variables and overall survival (OS). Methods: In a cohort of 92 GC patients who underwent gastrectomy, the characteristics of tumor core TLSs were assessed and the density of cytotoxic CD8+ T cells and regulatory FOXP3+ T cells was analyzed. Results: Patients with TLS had a better OS than patients without TLS, 19.4 months vs. 9.2 months (p = 0.001). Immature TLSs were more frequently associated with lymphovascular invasion and regional lymph node metastasis (p = 0.014 and p = 0.034). Mature TLSs had a higher FOXP3+ T lymphocyte density and lower CD8+/FOXP3+ ratio than immature TLSs (p = 0.029 and p = 0.013), and patients had a longer OS than patients with immature TLSs, 34.55 months vs. 15.2 months (p = 0.033). In patients with TLS-positive GC, cases with FOXP3+ T cells had a shorter OS, 12.7 months vs. 47.5 months (p < 0.001). Conclusions: The presence of FOXP3+ cells in TLS is associated with significantly shorter OS of patients with local/locally advanced GC. Full article
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15 pages, 1317 KB  
Article
Entosis in Colorectal, Lung, and Breast Cancer: Associations with Clinicopathological Features, Patient Outcomes, and Copy Number Alteration Landscape
by Ksenia A. Gaptulbarova, Sergey V. Vtorushin, Marina K. Ibragimova, Irina A. Tsydenova, Natalia A. Tarabanovskaya, Vitaly P. Shubin, Aleksey S. Tsukanov, Evgeny O. Rodionov, Sergey I. Achkasov and Nikolai V. Litviakov
J. Mol. Pathol. 2026, 7(1), 12; https://doi.org/10.3390/jmp7010012 - 17 Mar 2026
Viewed by 134
Abstract
Objective: This study examined the frequency of entosis in solid tumors of various origins (colorectal cancer, breast cancer, and lung cancer) and its association with clinical and pathological characteristics. It also examined survival and copy number alterations (CNAs) in genes associated with [...] Read more.
Objective: This study examined the frequency of entosis in solid tumors of various origins (colorectal cancer, breast cancer, and lung cancer) and its association with clinical and pathological characteristics. It also examined survival and copy number alterations (CNAs) in genes associated with stem cells. The aim was to assess the potential prognostic value of entotic events in tumors. Methods: A total of 238 patients were included: 96 with colorectal cancer (CRC), 45 with lung cancer (LC), and 97 with breast cancer (BC). Entotic cell-in-cell (CIC) structures were evaluated on hematoxylin–eosin–stained slides using Mackay’s criteria. A CIC frequency >0.1 per 20 high-power fields was considered positive. Clinicopathological parameters, overall survival (CRC), metastasis-free survival (LC and BC), and CNA profiles of stemness-related genes were analyzed. Amplifications of MAP1LC3A and other chromosomal loci were assessed. Results: CRC demonstrated the highest entosis rate, more than two-fold higher compared with BC and LC (p < 0.05). Entosis correlated with high tumor grade (G3) in CRC (p = 0.03). In LC, CIC-positive tumors were more frequent in patients with lymph-node metastases (p = 0.02), whereas in BC, the opposite trend was observed (p = 0.02). It was noted that in patients with stage III–IV LC, the frequency of entosis was significantly higher than in patients with stage I–II cancer (p = 0.03). CIC-positive status was associated with poorer overall survival in CRC (p = 0.03) and reduced metastasis-free survival in LC (p = 0.011). In breast cancer, no statistically significant survival differences were observed. Tumors harboring two or more stemness-gene amplifications showed significantly higher entosis frequency regardless of tumor site. A strong association was identified between entosis and MAP1LC3A amplification. Conclusions: Enosis is not a random morphological phenomenon but a process associated with unfavorable tumor characteristics, high malignancy, reduced survival, and amplification of stem cell-related genes. The results of this study confirm the working hypothesis that entosis may contribute to the emergence of aneuploid clones of tumor cells, including those containing amplifications of stem cell-associated genes. This positions entosis as a potential factor in tumor genetic heterogeneity, which is particularly important in the context of therapeutic selection pressure. The observed association between high entosis frequency and the presence of ≥2 stem cell gene amplifications, as well as its association with poor prognosis in colorectal and lung cancer, highlights its potential value as a prognostic indicator. Furthermore, MAP1LC3A amplification data may serve as a molecular marker of entotic activity and a potential therapeutic target. Full article
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28 pages, 1284 KB  
Article
Prognostic Factors of Survival in Patients with Surgically Treated Penile Squamous Cell Carcinoma: A Retrospective Cohort Analysis
by Andrei Andreșanu, Constantin Gîngu, Dragoș Eugen Georgescu, Mihaela Roxana Oliță, Mihai Adrian Dobra, Cristian Mirvald, Bogdan Obrișcă, Mihai-Adrian Eftimie and Ioanel Sinescu
Cancers 2026, 18(6), 952; https://doi.org/10.3390/cancers18060952 - 14 Mar 2026
Viewed by 159
Abstract
Background/Objectives: Penile squamous cell carcinoma (PSCC) is a rare malignancy with a potential major impact on survival. Prognostic assessment remains challenging, particularly in underrepresented eastern European populations, where region-specific evidence is lacking. This paper aimed to identify independent predictors of overall survival [...] Read more.
Background/Objectives: Penile squamous cell carcinoma (PSCC) is a rare malignancy with a potential major impact on survival. Prognostic assessment remains challenging, particularly in underrepresented eastern European populations, where region-specific evidence is lacking. This paper aimed to identify independent predictors of overall survival in surgically treated patients with PSCC from a Romanian high-volume tertiary center. Methods: This retrospective cohort study analyzed 60 patients who were surgically treated for PSCC between October 2020 and December 2024. Univariate and multivariate Cox proportional hazards regression analyses were performed to identify independent prognostic factors. Results: The mean patient age was 62 ± 12 years. T-stage distribution showed 30% pT1, 35% pT2, 31.67% pT3, and 3.33% pT4, with 55% of patients presenting with nodal metastases. Univariate analyses demonstrated significant associations between lymphovascular invasion (p < 0.001), perineural invasion (p = 0.022), and positive surgical margins (p = 0.030) and risk of death. Multivariate analysis identified three independent prognostic factors: absence of histologically documented urethral invasion (HR 0.32; p = 0.027), T3–T4 disease (HR 8.26; p = 0.005 vs. T1), and N3 stage (HR 3.53; p = 0.030 vs. N0–N1). Patients without urethral invasion demonstrated significantly longer median overall survival (63 months vs. 11 months). The final three-variable prognostic model demonstrated good discrimination (C-index 0.78), providing a potential practical risk stratification tool. Conclusions: Urethral invasion, advanced T-stage, and N3 disease independently predict poor survival in surgically treated PSCC. The identification of urethral invasion as an independent prognostic factor warrants consideration in clinical practice. This is the first study of a Romanian cohort to provide critical data for risk-adapted treatment strategies in underrepresented eastern European populations. Full article
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31 pages, 695 KB  
Review
Lymph Node Metastasis in Head and Neck Squamous Cell Carcinoma: Evolving Prognostic Markers, Molecular Insights, and Implications for Precision Staging
by Andrés Coca-Pelaz, Ehab Y. Hanna, Orlando Guntinas-Lichius, Luiz P. Kowalski, Juan Pablo Rodrigo, Robert P. Takes, Marc Hamoir, Remco de Bree, Francisco J. Civantos, K. Thomas Robbins, Carlos Suárez, M. P. Sreeram, Karthik Rao and Alfio Ferlito
Diagnostics 2026, 16(6), 855; https://doi.org/10.3390/diagnostics16060855 - 13 Mar 2026
Viewed by 472
Abstract
Lymph node metastasis (LNM) is one of the most powerful prognostic determinants in head and neck squamous cell carcinoma (HNSCC). The extent and pattern of nodal involvement critically influence staging accuracy, therapeutic decision-making, and patient outcomes. However, the biological and clinical implications of [...] Read more.
Lymph node metastasis (LNM) is one of the most powerful prognostic determinants in head and neck squamous cell carcinoma (HNSCC). The extent and pattern of nodal involvement critically influence staging accuracy, therapeutic decision-making, and patient outcomes. However, the biological and clinical implications of nodal disease remain complex and continue to evolve. We aim to synthesize current clinical and translational evidence regarding the prognostic and therapeutic impact of LNM in HNSCC and to highlight emerging trends relevant to precision staging. A narrative review was conducted through a structured literature search in PubMed and Scopus (2008–2025), with emphasis on studies published in the last five years. Meta-analyses, large cohort studies, and evidence-based guidelines addressing prognostic factors, biological mechanisms, and management strategies were critically appraised. LNM is consistently associated with reduced overall and disease-free survival across major head and neck subsites. Key independent prognostic variables include the number of metastatic nodes, extranodal extension, and involved cervical levels. Recent advances, such as refinements in the AJCC 8th edition, sentinel lymph node mapping, high-resolution imaging, and molecular profiling, have improved early detection and refined risk stratification. LNM remains central to prognostic evaluation and treatment selection in HNSCC. Integrating biological insights with molecular diagnostics and advanced imaging will be essential to achieving precision staging and individualized therapeutic strategies. Full article
(This article belongs to the Special Issue Clinical Diagnosis of Otorhinolaryngology)
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14 pages, 1442 KB  
Article
Deep Learning-Driven Pathological Prediction of Lymph Node Metastasis in Patients with Head and Neck Squamous Cell Carcinoma Using Primary Whole Slide Images
by Zaizai Cao, Zhe Chen, Jiangtao Zhong, Hengchao Chen, Ziming Fu, Zuning Shi, Jingyao Chen, Yajun Yu and Shuihong Zhou
Cancers 2026, 18(6), 933; https://doi.org/10.3390/cancers18060933 - 13 Mar 2026
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Abstract
Background/Objectives: Accurate preoperative prediction of cervical lymph node metastasis (LNM) in head and neck squamous cell carcinoma (HNSCC) remains a major clinical challenge. This study aimed to develop a deep learning-based whole-slide image (WSI) model and an integrated nomogram to improve individualized LNM [...] Read more.
Background/Objectives: Accurate preoperative prediction of cervical lymph node metastasis (LNM) in head and neck squamous cell carcinoma (HNSCC) remains a major clinical challenge. This study aimed to develop a deep learning-based whole-slide image (WSI) model and an integrated nomogram to improve individualized LNM risk stratification. Methods: A total of 355 formalin-fixed paraffin-embedded (FFPE) WSIs and 282 frozen WSIs from the TCGA-HNSC cohort, along with 329 FFPE WSIs from an external institutional cohort, were retrospectively analyzed. Tumor regions were annotated and tiled into standardized patches. A dual-stage multiple instance learning framework was applied to generate WSI-level predictions. A pathological risk score (path-score) was derived and combined with clinical variables to construct a predictive nomogram. Results: The WSI-level model outperformed patch-level classifiers, with the logistic regression-based model achieving area under the curve (AUC) values of 0.821 in the internal validation cohort and 0.730 in the external cohort. The path-score was independently associated with LNM. The integrated nomogram further improved discrimination, yielding AUCs of 0.865 and 0.786 in the internal and external cohorts, respectively. Calibration and decision curve analyses demonstrated good agreement and meaningful clinical benefit. Conclusions: This deep learning-driven pathology nomogram provides a robust and clinically applicable tool for preoperative prediction of cervical lymph node metastasis in HNSCC. Full article
(This article belongs to the Section Methods and Technologies Development)
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7 pages, 3080 KB  
Case Report
Urothelial Carcinoma of the Bladder with a Single Pancreatic Metastasis: A Case Report
by Benedetto Calabrese, Nicola Frego, Vittorio Fasulo, Mauro Sollai Pinna and Gianluigi Taverna
Reports 2026, 9(1), 81; https://doi.org/10.3390/reports9010081 - 10 Mar 2026
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Abstract
Background and Clinical Significance: Bladder cancer is common, with urothelial carcinoma (UC) comprising most cases in Western countries. Metastases usually involve pelvic structures, lymph nodes, and organs such as the liver, lungs, bones, and adrenal glands. Identifying unusual metastatic sites is critical [...] Read more.
Background and Clinical Significance: Bladder cancer is common, with urothelial carcinoma (UC) comprising most cases in Western countries. Metastases usually involve pelvic structures, lymph nodes, and organs such as the liver, lungs, bones, and adrenal glands. Identifying unusual metastatic sites is critical for accurate diagnosis and treatment planning. Case Presentation: A 65-year-old man with a history of high-grade (G3) UC and carcinoma in situ, previously treated with TURBT, second-look resection, and SWOG-protocol BCG, presented with a new bladder lesion (pT1). Staging CT revealed extravesical spread and a 1.5 cm pancreatic body nodule. EUS-guided biopsy confirmed metastatic UC with concordant immunohistochemistry (GATA3+), excluding primary pancreatic cancer. The patient was referred for systemic therapy with immune checkpoint inhibitors and Enfortumab Vedotin. Conclusions: This case demonstrates the rare occurrence of pancreatic metastasis from bladder UC. EUS-guided biopsy with immunohistochemistry is essential to distinguish secondary lesions from primary pancreatic tumors. Accurate diagnosis is crucial to guide systemic therapy, particularly with emerging immunotherapy and antibody–drug conjugates. Full article
(This article belongs to the Section Nephrology/Urology)
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22 pages, 938 KB  
Review
The Lymphatic–Bone Axis in Cancer Metastasis
by Ahlim Lee, James Rhee, Rajeev Malhotra, Jang Hee Han and Kangsan Roh
Cancers 2026, 18(6), 892; https://doi.org/10.3390/cancers18060892 - 10 Mar 2026
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Abstract
Bone metastasis is a devastating complication of advanced osteotropic malignancies, notably breast, prostate, lung carcinomas, and malignant melanoma, and remains a primary driver of mortality. Historical paradigms have conceptualized skeletal dissemination almost exclusively as a hematogenous process wherein circulating tumor cells colonize receptive [...] Read more.
Bone metastasis is a devastating complication of advanced osteotropic malignancies, notably breast, prostate, lung carcinomas, and malignant melanoma, and remains a primary driver of mortality. Historical paradigms have conceptualized skeletal dissemination almost exclusively as a hematogenous process wherein circulating tumor cells colonize receptive bone marrow niches. However, this model fails to reconcile why lymph node metastasis consistently serves as a potent predictor of bone involvement even though therapeutic lymphadenectomy rarely prevents distant spread. This discordance suggests that lymph nodes function not merely as passive reservoirs but as active ‘evolutionary gateways’ that sculpt bone-tropic metastatic clones. In this review, we introduce the Lymphatic–Bone Axis, a framework integrating lymphatic biology into models of bone metastasis. We synthesize emerging evidence elucidating how the lymph node microenvironment primes tumor cells through CCR7-CXCR4 switching, induction of osteomimicry programs, and metabolic reprogramming that favors survival within the bone marrow. We also discuss preclinical data demonstrating direct intranodal intravasation via high endothelial venules (HEVs), providing a rapid route into the systemic circulation that bypasses the thoracic duct. Beyond consolidating current knowledge, we outline a research agenda for dissecting this axis, including longitudinal single-cell transcriptomic mapping and functional assessments of lymph node-derived tumor cells. Finally, we consider translational implications, highlighting why bone-targeted agents alone may prove insufficient once cells are conditioned within lymphatic niches. By mechanistically linking lymphatic priming to skeletal colonization, this review informs the rational design of multimodal therapeutic approaches that jointly target lymphatic transit and the bone microenvironment. Full article
(This article belongs to the Special Issue Advances in Bone Metastasis Research: From Mechanisms to Therapy)
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31 pages, 8029 KB  
Article
A Novel Fluorescence-Triggered Auditory Feedback Photosensor for Precision Lymph Node Mapping
by Kicheol Yoon, Hyunjun Son, Hari Kang, Sangyun Lee, Tae-Hyeon Lee, Won-Suk Lee and Kwang Gi Kim
Sensors 2026, 26(6), 1745; https://doi.org/10.3390/s26061745 - 10 Mar 2026
Viewed by 233
Abstract
Background: In cancer surgery, resection of the primary tumor and regional lymph nodes (LNs) is critical. Adequate LN examination is essential to detect metastasis, which determines the cancer stage. Fluorescence emission allows for visual differentiation and rapid monitoring of LNs. Methods: [...] Read more.
Background: In cancer surgery, resection of the primary tumor and regional lymph nodes (LNs) is critical. Adequate LN examination is essential to detect metastasis, which determines the cancer stage. Fluorescence emission allows for visual differentiation and rapid monitoring of LNs. Methods: Cancer tissue is stained with a fluorescent dye (indocyanine green, ICG) to identify LNs. Fluorescence is induced from the stained LNs using LED light, and a photosensor coupled with a speaker detects the fluorescence signal and triggers an audible alarm. Filters are applied to prevent false alarms. Results: Upon LN detection, an alarm is emitted from the speaker, and the results are recorded using the LED and a digital multimeter (DMM). In clinical trials, ICG is injected to induce LN fluorescence staining, followed by LED irradiation to induce the fluorescent wavelength and verify LN imaging. Discussion: In clinical trials, ICG stains both LNs and blood vessels, which may lead to false positives. To address this limitation, artificial intelligence algorithms can be trained to specifically identify LNs. Conclusions: Detection of fluorescence wavelengths via photosensors allows for rapid identification of LNs, confirmed through an audible alarm, thereby reducing surgical time. This method shows potential for broad application in cancer surgery. Full article
(This article belongs to the Collection Biomedical Imaging and Sensing)
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