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Keywords = pathological site classification

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14 pages, 1522 KB  
Article
Calcaneal Spurs in Thai Skeletons: High Prevalence and Population-Specific Patterns for Forensic Identification
by Phatthiraporn Aorachon, Tarinee Sawatpanich, Suthat Duangchit, Chanasorn Poodendaen and Sitthichai Iamsaard
Forensic Sci. 2026, 6(1), 30; https://doi.org/10.3390/forensicsci6010030 - 9 Mar 2026
Viewed by 258
Abstract
Background/Objectives: Calcaneal spurs are pathological bone formations at entheseal attachment sites with clinical implications but limited forensic anthropological applications. While entheseal changes have been proposed as age estimation markers in forensic contexts, empirical validation remains insufficient, particularly for Southeast Asian populations. This study [...] Read more.
Background/Objectives: Calcaneal spurs are pathological bone formations at entheseal attachment sites with clinical implications but limited forensic anthropological applications. While entheseal changes have been proposed as age estimation markers in forensic contexts, empirical validation remains insufficient, particularly for Southeast Asian populations. This study evaluated calcaneal spur utility for forensic age estimation in Thai skeletal remains while establishing population-specific osteological reference data for forensic individuation. Materials and Methods: The 3516 dry calcanei from 1758 Northeastern Thai skeletons (1031 males, 727 females; age 22–106 years) were examined. Spurs were classified by anatomical location as dorsal (D-type), plantar (P-type), or combined plantar–dorsal (P–D type). The morphometric measurements were performed bilaterally. Age-associated patterns were analyzed across four age cohorts (≤40, 41–50, 51–60, ≥61 years), and Random Forest machine learning classification tested forensic age estimation capacity using 10-fold cross-validation. Results: Overall prevalence reached 67.63% with distinctive P–D type predominance. While age-stratified prevalence increased from 24.56% (≤40 years) to 74.77% (≥61 years), Random Forest modeling explicitly demonstrated overall classification accuracy of 62.5%. Compared between sexes, the maximum length of calcaneal spurs was significantly longer in males. Dimensional analyses revealed weak age correlations and substantial inter-individual morphological variation precluded reliable age prediction. Interestingly, the unique P–D type distribution pattern (77.5% among spur-bearing individuals) may serve as an auxiliary marker for Thai population affinity assessment in forensic contexts. Conclusions: This study established the first comprehensive Thai-specific osteological reference for calcaneal spurs, revealing distinctive plantar–dorsal type predominance valuable for forensic population affinity assessment and provided population-specific baseline data for forensic individuation. Full article
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22 pages, 3134 KB  
Article
Experimental Mis-Splicing Assessment and ACMG/AMP-Guided Classification of 47 ATM Splice-Site Variants
by Inés Llinares-Burguet, Lara Sanoguera-Miralles, Elena Bueno-Martínez, Ada Esteban-Sanchez, Daniel Romano-Medina, Lobna Ramadane-Morchadi, Alicia García-Álvarez, Pedro Pérez-Segura, Doug F. Easton, Peter Devilee, Maaike P. G. Vreeswijk, Miguel de la Hoya and Eladio A. Velasco-Sampedro
Int. J. Mol. Sci. 2026, 27(2), 765; https://doi.org/10.3390/ijms27020765 - 12 Jan 2026
Viewed by 741
Abstract
Pathogenic germline variants in the ATM gene are associated with a 20–30% lifetime risk of breast cancer. Crucially, a relevant fraction of loss-of-function variants in breast cancer susceptibility genes disrupts pre-mRNA splicing. We aimed to perform splicing analysis of ATM splice-site variants identified [...] Read more.
Pathogenic germline variants in the ATM gene are associated with a 20–30% lifetime risk of breast cancer. Crucially, a relevant fraction of loss-of-function variants in breast cancer susceptibility genes disrupts pre-mRNA splicing. We aimed to perform splicing analysis of ATM splice-site variants identified in the large-scale sequencing project BRIDGES (Breast Cancer After Diagnostic Gene Sequencing). To this end, we bioinformatically selected 47 splice-site variants across 17 exons that were genetically engineered into three minigenes and assayed in MCF-7 cells. Aberrant splicing was observed in 38 variants. Of these, 30 variants, including 7 missense, yielded no or negligible expression of the minigene full-length (mgFL) transcript. A total of 69 different transcripts were characterized, 48 of which harboured a premature termination codon. Some variants, such as c.2922-1G>A, generated complex patterns with up to 10 different transcripts. Alternative 3′ or 5′ splice-site usage was the predominant event. Integration of ATM minigene read-outs into the ACMG/AMP (American College of Medical Genetics and Genomics/Association for Molecular Pathology)-based specifications for the ATM gene enabled the classification of 30 ATM variants as pathogenic or likely pathogenic and 9 as likely benign. Overall, splicing assays provide key information for variant interpretation and the clinical management of patients. Full article
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29 pages, 2146 KB  
Review
Intestinal Mucin Glycosylation: Structural Regulation, Homeostasis Maintenance and Disease Association
by Yunye Li, Jia Pan, Huimin Liu and Chuanguo Liu
Biomolecules 2025, 15(11), 1552; https://doi.org/10.3390/biom15111552 - 5 Nov 2025
Cited by 7 | Viewed by 3369
Abstract
The intestinal barrier is a complex configuration that defends against external assaults and maintains intestinal health. Disruption of barrier function can lead to intestinal inflammation and various diseases. Mucins are the primary structural components of the intestinal barrier, and their extensive glycosylation is [...] Read more.
The intestinal barrier is a complex configuration that defends against external assaults and maintains intestinal health. Disruption of barrier function can lead to intestinal inflammation and various diseases. Mucins are the primary structural components of the intestinal barrier, and their extensive glycosylation is critical for their protective function. Mucin glycans enhance the physicochemical integrity of the mucus barrier, protect against enzymatic degradation, modulate host immune responses, and shape the gut microbiota by providing adhesion sites and selective nutrient sources. While proper glycosylation maintains barrier integrity, supports a balanced microbial ecosystem, and limits unnecessary immune activation, its disruption leads to compromised barrier function, microbial dysbiosis, increased intestinal permeability, and ultimately contributes to the development of chronic colitis and colorectal cancer. Therefore, mucin glycosylation plays a crucial role in preserving intestinal barrier integrity and preventing colonic diseases. This review summarizes the classifications and structural features of intestinal mucin glycosylation, elucidates their roles in maintaining barrier function and their pathological alterations in intestinal disorders, and highlights the implications of mucin glycosylation for precision diagnosis and targeted therapy of intestinal diseases. Full article
(This article belongs to the Section Molecular Biology)
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11 pages, 1535 KB  
Article
Helicobacter pylori-Associated Infection: A Comprehensive Histopathological Analysis of Gastric Biopsies from Patients of Pakistan
by Obaid Ullah, Hazir Rahman and Salma Ijaz
Microbiol. Res. 2025, 16(11), 232; https://doi.org/10.3390/microbiolres16110232 - 2 Nov 2025
Viewed by 2131
Abstract
Helicobacter pylori is a gastric pathogen that induces chronic gastritis, which may progress to neutrophilic activity, glandular atrophy, intestinal metaplasia, and gastric carcinoma. The aim of this study was to evaluate H. pylori-induced tissue damage. A total of 602 gastric biopsy samples [...] Read more.
Helicobacter pylori is a gastric pathogen that induces chronic gastritis, which may progress to neutrophilic activity, glandular atrophy, intestinal metaplasia, and gastric carcinoma. The aim of this study was to evaluate H. pylori-induced tissue damage. A total of 602 gastric biopsy samples were collected, categorized, and analyzed using hematoxylin and eosin and Giemsa staining, followed by molecular confirmation through PCR targeting the species-specific 16S rRNA gene. H. pylori density and histopathological features were evaluated and graded according to the updated Sydney classification system. H. pylori was detected in 55% (n = 334) of cases, and the antrum (50.83%, p < 0.00001) was the predominant site. A slightly higher prevalence was observed in females, accounting for 56.9% compared to males at 43.1%, which was attributed to sociocultural exposure differences. Individuals aged 11–40 years accounted for 58.3% (n = 195), highlighting early-age acquisition of infection. H. pylori infection was significantly linked to moderate-to-severe inflammation (63.2%, p < 0.00001) and neutrophilic activity (53.3%, p < 0.00001). Intestinal metaplasia and atrophy were infrequent, present in 0.6% (95% CI, 0.02, p = 0.149) and 0.9% (95% CI, 0.05, p = 0.430) of individuals. H. pylori infection causes chronic inflammation and neutrophilic infiltration of the stomach mucosa. Early identification and histopathological examination are essential in assessing H. pylori-related gastric pathology. Full article
(This article belongs to the Special Issue Host–Microbe Interactions in Health and Disease)
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18 pages, 1328 KB  
Article
Endoscopic and Pathological Examinations of Early-Signet-Ring Carcinoma in the Stomach
by Zhao Liang, Liang Zheng and Jia Cao
Healthcare 2025, 13(21), 2689; https://doi.org/10.3390/healthcare13212689 - 23 Oct 2025
Viewed by 1723
Abstract
Objective: Early-signet-ring cell carcinoma has a low malignancy and good prognosis, while advanced signet-ring cell carcinoma has high malignancy and high mortality. So, we need to understand the risk factors of early-signet-ring cell carcinoma, analyze the relationship between early gastric signet-ring cell carcinoma [...] Read more.
Objective: Early-signet-ring cell carcinoma has a low malignancy and good prognosis, while advanced signet-ring cell carcinoma has high malignancy and high mortality. So, we need to understand the risk factors of early-signet-ring cell carcinoma, analyze the relationship between early gastric signet-ring cell carcinoma and non-Signet-ring cell carcinoma, and between pure signet-ring cell carcinoma and mixed signet-ring cell carcinoma, in order to provide the basis for the early diagnosis and treatment of signet-ring cell carcinoma. Methods: In this study, a retrospective analysis of 424 cases of early gastric cancer that underwent endoscopic submucosal dissection and surgical treatment between March 2019 and March 2023 in Shanghai Oriental Hospital was carried out. Among the cases, the two groups, namely, the signet-ring cell carcinoma and non-signet-ring cell carcinoma group, and the pure signet-ring cell carcinoma and mixed signet-ring cell carcinoma group, were compared and analyzed. With the help of logistic regression analysis, gender, age, smoking history, alcohol consumption history, tumor site, pathological characteristics, disease progression, tumor size, infiltration depth, and H. pylori infection were investigated between the two groups. Result: The results of the univariate regression analyses in the signet-ring cell carcinoma and non-signet-ring cell carcinoma groups showed that being female (p = 0.001), age < 60 years (p = 0.001), with cancer foci in the middle part of the stomach (p = 0.001), and with a mixed type of cancer foci (p = 0.007) were the risk factors for signet-ring cell carcinoma. In the multifactorial regression analysis, age < 60 years (OR = 1.037, CL = 1.008–1.067, p = 0.012), cancer foci in the middle part of the stomach (OR = 2.094, CL = 1.488–2.948, p = 0.001), mixed-type patients (OR = 0.702, CL = 0.519–0.951, p = 0.022), and women (OR = 0.421, CL = 0.254–0.698, p = 0.001) were the risk factors for signet-ring cell cancer. These are independent risk factors for signet-ring cell carcinoids. Univariate regression analysis on the pure and mixed signet-ring cell carcinoma groups showed that Helicobacter pylori infection (p = 0.001), Kimura–Takemoto classification O1–O3 (p = 0.013), flat and concave types (p = 0.004), and age < 60 years (p = 0.013) were risk factors affecting the development of pure signet-ring cell carcinoma. In the multifactorial regression analysis, age (OR = 0.233, CL = 0.059–0.930, p = 0.039) was the main independent risk factor for pure signet-ring cell carcinoma. Conclusions: Age < 60 years, cancer foci located in the middle of the stomach, mixed type, and female are associated with the development of early gastric signet-ring cell carcinoma; age < 60 years is related to the development of pure signet-ring cell carcinoma, so we need to pay attention to these clinical and pathological factors to prevent the growth of ring cell carcinoma. Full article
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12 pages, 269 KB  
Article
The Effect of HER2 Status on Gastric Cancer Survival and the Clinical Implications of the HER2-Low Definition: A Retrospective Study
by Mehmet Uzun, Savas Gokcek, Melis Kilinc, Ferhat Ekinci, Tugay Avci, Atike Pinar Erdogan, Elif Atag and Ilkay Tugba Unek
Medicina 2025, 61(9), 1675; https://doi.org/10.3390/medicina61091675 - 15 Sep 2025
Cited by 1 | Viewed by 1941
Abstract
Background and Objectives: HER-2 expression plays a critical role in the biological behavior and treatment of gastric cancer. With the emergence of HER-2-targeted therapies, classification into negative, low, and positive groups has gained clinical importance. The present study focused on assessing the [...] Read more.
Background and Objectives: HER-2 expression plays a critical role in the biological behavior and treatment of gastric cancer. With the emergence of HER-2-targeted therapies, classification into negative, low, and positive groups has gained clinical importance. The present study focused on assessing the link between HER-2 status and clinical–pathological variables, metastatic involvement, and overall survival (OS) among advanced gastric cancer patients. Materials and Methods: A total of 300 patients with advanced gastric adenocarcinoma were retrospectively analyzed. The mean age of the 300 patients included in the study was 61.8 years, and 70% of them were male. Based on immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), patients were classified as HER-2-negative (IHC 0), HER-2-low (IHC 1+ or 2+/FISH-negative), or HER-2-positive (IHC 3+ or 2+/FISH-positive). Clinicopathological variables, metastatic sites, and OS were compared among groups using Pearson’s Chi-square, Fisher’s exact test, ANOVA, and Kaplan–Meier survival analysis. Results: Significant differences were observed among HER-2 subgroups in pathological subtype (p = 0.006), liver metastasis (p = 0.009), lung metastasis (p = 0.006), and other metastatic sites (p = 0.001). HER-2-positive patients demonstrated higher rates of adenocarcinoma histology and increased liver and lung metastases. In female patients, HER-2 status was significantly associated with lung (p = 0.001) and other metastases (p < 0.001). Median OS for the entire cohort was 9.83 months (95% CI: 8.29–11.36). HER-2-positive patients had a significantly longer OS (15.06 months) compared with HER-2-negative patients (8.73 months; p = 0.039). Conclusions: HER-2 status is an important predictor of metastatic behavior and survival in advanced gastric cancer. HER-2-positive patients display distinct metastatic patterns and improved outcomes, supporting the value of HER-2-targeted therapies. The HER-2-low group may represent a biologically and clinically relevant intermediate subtype requiring further investigation. Full article
(This article belongs to the Special Issue Prophylaxis, Diagnosis, and Treatment Strategies of Gastric Cancer)
20 pages, 7967 KB  
Article
OCT-Based Morphological Classification of Healed Coronary Plaques: Insights from Imaging of Fresh Thrombi at Different Stages of Healing and Implications for Post-Stenting Edge Dissections
by Calin Homorodean, Horea-Laurentiu Onea, Florin-Leontin Lazar, Mihai Claudiu Ober, Mihail Spinu, Dan-Alexandru Tataru, Maria Olinic, Ioana Rada Popa Ilie, Romana Homorodean, Daniel-Corneliu Leucuta and Dan-Mircea Olinic
Medicina 2025, 61(8), 1440; https://doi.org/10.3390/medicina61081440 - 10 Aug 2025
Viewed by 1739
Abstract
Background and Objectives: In vivo data on healed coronary plaques (HCPs), the hallmark of previous plaque disruption, remains scarce. The study aimed to use optical coherence tomography (OCT) imaging to assess the prevalence, morphological features, and clinical significance of culprit HCPs in [...] Read more.
Background and Objectives: In vivo data on healed coronary plaques (HCPs), the hallmark of previous plaque disruption, remains scarce. The study aimed to use optical coherence tomography (OCT) imaging to assess the prevalence, morphological features, and clinical significance of culprit HCPs in patients with acute coronary syndrome (ACS). Materials and Methods: A total of 87 ACS patients (74.3% non-ST-segment elevation ACS) who underwent pre-procedural OCT imaging of the culprit vessel at a single center were retrospectively analyzed. A pilot subgroup of patients with intracoronary thrombi at the culprit site, in various stages of organization and healing, enabled a detailed morphological characterization of HCP despite the absence of histological validation. Three distinct HCP imaging aspects were identified: type I—overlaying fibrous tissue, type II—overlaying lipid tissue, and type III—overlaying calcific tissue. HCP presence was subsequently assessed in the entire population. Clinical correlations included associations with post-stenting outcomes, particularly edge dissections (ED). Results: Culprit HCPs were identified in 78 patients (89.7%): type I—30.8%, type II—51.3%, and type III—17.9%. Regarding the underlying substrate and complication mechanism, type I HCP was associated with pathological intimal thickening (70.8%) and plaque erosion (75%), type II with lipid-rich plaque (80%) and plaque rupture (PR) (82.5%), and type III correlated with calcific plaque (92.9%, p < 0.0001) and both PR and calcified nodule (p < 0.0001). A unique signal-rich ring was observed at the HCP–tissue interface in both type II (77.5%) and type III (78.6%, p < 0.0001). There was a significant correlation between stent ED and HCP presence at landing zones (LZ) (HR 4.14, 95% CI: 1.79–9.55; p < 0.001). Conclusions: OCT analysis of intracoronary organizing fresh thrombi allowed detailed characterization of culprit HCPs and in vivo classification into three imaging types. This approach likely contributed to the high observed detection rate of HCP by enhancing recognition of subtle OCT features. HCP may create mechanical vulnerability if located at the stent LZ. Our improved HCP detection techniques may help optimize stent-related outcomes of OCT-guided procedures by choosing an HCP-free LZ or longer stents. Full article
(This article belongs to the Special Issue Recent Advances in Interventional Cardiology)
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21 pages, 2994 KB  
Article
A Multi-Omics Integration Framework with Automated Machine Learning Identifies Peripheral Immune-Coagulation Biomarkers for Schizophrenia Risk Stratification
by Feitong Hong, Qiuming Chen, Xinwei Luo, Sijia Xie, Yijie Wei, Xiaolong Li, Kexin Li, Benjamin Lebeau, Crystal Ling, Fuying Dao, Hao Lin, Lixia Tang, Mi Yang and Hao Lv
Int. J. Mol. Sci. 2025, 26(15), 7640; https://doi.org/10.3390/ijms26157640 - 7 Aug 2025
Cited by 5 | Viewed by 2968
Abstract
Schizophrenia (SCZ) is a complex psychiatric disorder with heterogeneous molecular underpinnings that remain poorly resolved by conventional single-omics approaches, limiting biomarker discovery and mechanistic insights. To address this gap, we applied an artificial intelligence (AI)-driven multi-omics framework to an open access dataset comprising [...] Read more.
Schizophrenia (SCZ) is a complex psychiatric disorder with heterogeneous molecular underpinnings that remain poorly resolved by conventional single-omics approaches, limiting biomarker discovery and mechanistic insights. To address this gap, we applied an artificial intelligence (AI)-driven multi-omics framework to an open access dataset comprising plasma proteomics, post-translational modifications (PTMs), and metabolomics to systematically dissect SCZ pathophysiology. In a cohort of 104 individuals, comparative analysis of 17 machine learning models revealed that multi-omics integration significantly enhanced classification performance, reaching a maximum AUC of 0.9727 (95% CI: 0.8889–1.000) using LightGBMXT, compared to 0.9636 (95% CI: 0.8636–1.0000) with CNNBiLSTM for proteomics alone. Interpretable feature prioritization identified carbamylation at immunoglobulin-constant region sites IGKC_K20 and IGHG1_K8, alongside oxidation of coagulation factor F10 at residue M8, as key discriminative molecular events. Functional analyses identified significantly enriched pathways including complement activation, platelet signaling, and gut microbiota-associated metabolism. Protein interaction networks further implicated coagulation factors F2, F10, and PLG, as well as complement regulators CFI and C9, as central molecular hubs. The clustering of these molecules highlights a potential axis linking immune activation, blood coagulation, and tissue homeostasis, biological domains increasingly recognized in psychiatric disorders. These results implicate immune–thrombotic dysregulation as a critical component of SCZ pathology, with PTMs of immune proteins serving as quantifiable disease indicators. Our work delineates a robust computational strategy for multi-omics integration into psychiatric research, offering biomarker candidates that warrant further validation for diagnostic and therapeutic applications. Full article
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14 pages, 631 KB  
Article
Evaluation of Navify Mutation Profiler Tertiary Analysis Software Assessing for Hematologic Malignancies
by Ruby Singhrao, Michael J. Clark, Shikha Chugh, Lisha Capucion, Shuba Krishna, Ranga Yerram, Lili Niu, Adama Parham, Amy Harrell, John Duncan, Kristina Clark and Manana Javey
J. Mol. Pathol. 2025, 6(2), 9; https://doi.org/10.3390/jmp6020009 - 22 May 2025
Viewed by 2046
Abstract
Background: Navify® Mutation Profiler (Navify MP) is a cloud-based, tertiary analysis software that provides curation, annotation, and reporting of somatic genomic alterations and biomarker signatures identified by next-generation sequencing. The Navify MP software leverages Association for Molecular Pathology/American Society of Clinical Oncology/College [...] Read more.
Background: Navify® Mutation Profiler (Navify MP) is a cloud-based, tertiary analysis software that provides curation, annotation, and reporting of somatic genomic alterations and biomarker signatures identified by next-generation sequencing. The Navify MP software leverages Association for Molecular Pathology/American Society of Clinical Oncology/College of American Pathologists (AMP/ASCO/CAP) Somatic Variant Classification Guidelines to provide information on detected somatic genomic variants and associated therapies according to region-specific approvals. Methods: This validation study assessed the accuracy of the Navify MP software and curation process for hematologic malignancies as compared to expert opinion. A total of 86 variants derived from hematologic malignancies (including myeloid and lymphoid leukemias, B cell lymphomas, and multiple myeloma) were used to contrive 12 VCF files. The VCFs were made up of the following classes of genomic alterations: single nucleotide variants, small insertions and deletions, fusions, and copy number alterations. Of the 86 variants, 42 were Tier IA, and 44 were non-Tier IA, based on AMP/ASCO/CAP classification. The study was performed at four sites with seven software users (molecular genetics experts). Results: Tier classification agreement between Navify MP and expert user assignment was 91.34% for Tier IA and 95.02% across all hematologic variants. The agreement on associated therapies for the Navify MP-classified Tier IA hematologic variants was 99.08%. Conclusions: Navify MP is a robust automated solution for genomic variant reporting of hematologic malignancies and remains up to date with evolving regional approvals and medical guidelines. Full article
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11 pages, 276 KB  
Article
Evaluation of Periodontitis and Fusobacterium nucleatum Among Colorectal Cancer Patients: An Observational Cross-Sectional Study
by Anna Antonacci, Cinzia Bizzoca, Giuseppe Barile, Valeria Andriola, Leonardo Vincenti, Nicola Bartolomeo, Antonia Abbinante, Germano Orrù and Massimo Corsalini
Healthcare 2024, 12(21), 2189; https://doi.org/10.3390/healthcare12212189 - 4 Nov 2024
Cited by 2 | Viewed by 2355
Abstract
Background: Periodontitis has been associated with an increased risk of CRC, as well as a worse prognosis due to increased inflammation mediators and carcinogenic factors. Moreover, direct and indirect virulence factors from periodontal pathogens, such as Fusobacterium nucleatum, could play a pivotal [...] Read more.
Background: Periodontitis has been associated with an increased risk of CRC, as well as a worse prognosis due to increased inflammation mediators and carcinogenic factors. Moreover, direct and indirect virulence factors from periodontal pathogens, such as Fusobacterium nucleatum, could play a pivotal role in malignant transformation and progression. This cross-sectional study aims to evaluate the presence and the stage of periodontitis in a cohort of patients with CRC. The secondary aim is to assess the presence of F. nucleatum and its relationship with patients’ general characteristics, concomitant pathologies, tumor characteristics, and drug therapy. Materials and Methods: Patients affected by CRC underwent dental examination and periodontal charting with the “North Carolina” probe to assess the presence and stage of periodontitis, according to the new classification of periodontal diseases of the World Workshop of the European Federation of Periodontology (EFP) and the American Academy of Periodontology (AAP) 2017. F. nucleatum presence was assessed by a dorsal tongue swab and related to the patient’s general characteristics, concomitant pathologies, tumor characteristics, and drug therapy. Results: Periodontal disease was found in 94.3% of I/II CRC stage patients and 100% of III/IV CRC stage patients. Severe periodontitis was found in 76% of the advanced CRC stage and 87.9% of patients with initial CRC, while initial periodontitis was found in 12.1% of initial CRC and 24% of late CRC stages, respectively, without significant differences. F. nucleatum presence showed no correlation between the patient’s and tumor’s characteristics, comorbidities, and drug assumed. Conclusions: Periodontal disease showed a high prevalence among CRC patients. Moreover, severe periodontitis has a higher prevalence in CRC patients compared to initial periodontitis. F. nucleatum presence was unrelated to CRC stage, site, other comorbidities, and drug therapies. With these data, it is not possible to admit a direct relationship between CRC and periodontal disease, but further case–control studies must be carried out to further prove this aspect. Preventive and operative targeted strategies to maintain a healthy oral status are suggested in CRC patients. Full article
13 pages, 2578 KB  
Article
Impact of Formalin- and Cryofixation on Raman Spectra of Human Tissues and Strategies for Tumor Bank Inclusion
by Giulia Mirizzi, Finn Jelke, Michel Pilot, Karoline Klein, Gilbert Georg Klamminger, Jean-Jacques Gérardy, Marily Theodoropoulou, Laurent Mombaerts, Andreas Husch, Michel Mittelbronn, Frank Hertel and Felix Bruno Kleine Borgmann
Molecules 2024, 29(5), 1167; https://doi.org/10.3390/molecules29051167 - 6 Mar 2024
Cited by 3 | Viewed by 2658
Abstract
Reliable training of Raman spectra-based tumor classifiers relies on a substantial sample pool. This study explores the impact of cryofixation (CF) and formalin fixation (FF) on Raman spectra using samples from surgery sites and a tumor bank. A robotic Raman spectrometer scans samples [...] Read more.
Reliable training of Raman spectra-based tumor classifiers relies on a substantial sample pool. This study explores the impact of cryofixation (CF) and formalin fixation (FF) on Raman spectra using samples from surgery sites and a tumor bank. A robotic Raman spectrometer scans samples prior to the neuropathological analysis. CF samples showed no significant spectral deviations, appearance, or disappearance of peaks, but an intensity reduction during freezing and subsequent recovery during the thawing process. In contrast, FF induces sustained spectral alterations depending on molecular composition, albeit with good signal-to-noise ratio preservation. These observations are also reflected in the varying dual-class classifier performance, initially trained on native, unfixed samples: The Matthews correlation coefficient is 81.0% for CF and 58.6% for FF meningioma and dura mater. Training on spectral differences between original FF and pure formalin spectra substantially improves FF samples’ classifier performance (74.2%). CF is suitable for training global multiclass classifiers due to its consistent spectrum shape despite intensity reduction. FF introduces changes in peak relationships while preserving the signal-to-noise ratio, making it more suitable for dual-class classification, such as distinguishing between healthy and malignant tissues. Pure formalin spectrum subtraction represents a possible method for mathematical elimination of the FF influence. These findings enable retrospective analysis of processed samples, enhancing pathological work and expanding machine learning techniques. Full article
(This article belongs to the Special Issue Past Present and Future of Raman Spectroscopy)
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16 pages, 1549 KB  
Article
A Descriptive Study of 103 Primary Cutaneous B-Cell Lymphomas: Clinical and Pathological Characteristics and Treatment from the Spanish Lymphoma Oncology Group (GOTEL)
by Natividad Martínez-Banaclocha, Francisca Martínez-Madueño, Berta Caballé, Joan Badia, Mar Blanes, David Aguiar Bujanda, Virginia Calvo, Jose Gómez Codina, Cristina Quero Blanco, Pablo Espinosa, Javier Lavernia, Francisco Ramón García Arroyo, María Guirado Risueño, Cristina Llorca, Raquel Cumeras, Mariano Provencio Pulla and Josep Gumà
Cancers 2024, 16(5), 1034; https://doi.org/10.3390/cancers16051034 - 3 Mar 2024
Cited by 6 | Viewed by 3283
Abstract
Primary cutaneous B-cell lymphomas (PCBCLs) are B-cell lymphomas that can occur in the skin without evidence of extracutaneous involvement. The 2005 WHO/EORTC classification of cutaneous lymphomas and its 2018 update have distinguished three main categories based on clinicopathological, immunohistochemical, and genetic characteristics: primary [...] Read more.
Primary cutaneous B-cell lymphomas (PCBCLs) are B-cell lymphomas that can occur in the skin without evidence of extracutaneous involvement. The 2005 WHO/EORTC classification of cutaneous lymphomas and its 2018 update have distinguished three main categories based on clinicopathological, immunohistochemical, and genetic characteristics: primary cutaneous marginal zone lymphoma (PCMZL), primary cutaneous follicle centre lymphoma (PCFCL), and primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT). PCMZL and PCFCL are clinically indolent, while PCDLBCL-LT is an aggressive lymphoma. Due to its low incidence and lack of prospective studies, it is difficult to establish a standard treatment for each subgroup. The objective of our study was to describe the clinical and pathological characteristics of 103 patients with cutaneous B-cell lymphoma from 12 centres belonging to the Spanish Lymphoma Oncology Group. The median age was 53 years (40–65). According to skin extension, 62% had single-site lymphoma, 17% had regional lymphoma, and 20% had multifocal lymphoma. Histology: 66% had PCMZL, 26% had PCFCL, and 8% had PCDLBCL-LT. Twenty-three percent of the patients were treated exclusively with surgery, 26% with radiotherapy only, 21% with surgery plus radiotherapy, 10% with polychemotherapy, and 5% with rituximab monotherapy. Overall, 96% of patients achieved a complete response, and 44% subsequently relapsed, most of them relapsing either locally or regionally. The 10-year OS was 94.5% for the entire cohort, 98% for the PCMZL cohort, 95% for the PCFCL cohort, and 85.7% for the PCDLBCL-LT cohort. Our data are comparable to those of other published series, except for the high frequency of PCMZL. The expected heterogeneity in therapeutic management has been observed. Full article
(This article belongs to the Section Cancer Pathophysiology)
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11 pages, 236 KB  
Article
Safety and Diagnostic Efficacy of Image-Guided Biopsy of Small Renal Masses
by Muhamad Serhal, Sean Rangwani, Stephen M. Seedial, Bartley Thornburg, Ahsun Riaz, Albert A. Nemcek, Kent T. Sato, Kent T. Perry, Bonnie Choy, Robert J. Lewandowski and Andrew C. Gordon
Cancers 2024, 16(4), 835; https://doi.org/10.3390/cancers16040835 - 19 Feb 2024
Cited by 9 | Viewed by 3210
Abstract
Introduction: Image-guided renal mass biopsy is gaining increased diagnostic acceptance, but there are limited data concerning the safety and diagnostic yield of biopsy for small renal masses (≤4 cm). This study evaluated the safety, diagnostic yield, and management after image-guided percutaneous biopsy for [...] Read more.
Introduction: Image-guided renal mass biopsy is gaining increased diagnostic acceptance, but there are limited data concerning the safety and diagnostic yield of biopsy for small renal masses (≤4 cm). This study evaluated the safety, diagnostic yield, and management after image-guided percutaneous biopsy for small renal masses. Methods: A retrospective IRB-approved study was conducted on patients who underwent renal mass biopsy for histopathologic diagnosis at a single center from 2015 to 2021. Patients with a prior history of malignancy or a renal mass >4 cm were excluded. Descriptive statistics were used to summarize patient demographics, tumor size, the imaging modality used for biopsy, procedure details, complications, pathological diagnosis, and post-biopsy management. A biopsy was considered successful when the specimen was sufficient for diagnosis without need for a repeat biopsy. Complications were graded according to the SIR classification of adverse events. A chi-squared test (significance level set at p ≤ 0.05) was used to compare the success rate of biopsies in different lesion size groups. Results: A total of 167 patients met the inclusion criteria. The median age was 65 years (range: 26–87) and 51% were male. The median renal mass size was 2.6 cm (range: one–four). Ultrasound was solely employed in 60% of procedures, CT in 33%, a combination of US/CT in 6%, and MRI in one case. With on-site cytopathology, the median number of specimens obtained per procedure was four (range: one–nine). The overall complication rate was 5%. Grade A complications were seen in 4% (n = 7), consisting of perinephric hematoma (n = 6) and retroperitoneal hematoma (n = 1). There was one grade B complication (0.5%; pain) and one grade D complication (0.5%; pyelonephritis). There was no patient mortality within 30 days post-biopsy. Biopsy was successful in 88% of cases. A sub-group analysis showed a success rate of 85% in tumors <3 cm and 93% in tumors ≥3 cm (p = 0.01). Pathological diagnoses included renal cell carcinoma (65%), oncocytoma (18%), clear cell papillary renal cell tumors (9%), angiomyolipoma (4%), xanthogranulomatous pyelonephritis (1%), lymphoma (1%), high-grade papillary urothelial carcinoma (1%), and metanephric adenoma (1%), revealing benign diagnosis in 30% of cases. The most common treatment was surgery (40%), followed by percutaneous cryoablation (22%). In total, 37% of patients were managed conservatively, and one patient received chemotherapy. Conclusion: This study demonstrates the safety and diagnostic efficacy of image-guided biopsy of small renal masses. The diagnostic yield was significantly higher for masses 3–4 cm in size compared to those <3 cm. The biopsy results showed a high percentage of benign diagnoses and informed treatment decisions in most patients. Full article
(This article belongs to the Collection Advances in Diagnostic and Interventional Radiology in Oncology)
14 pages, 4012 KB  
Article
The Clinical Implication of Conversion Surgery in Patients with Stage IV Gastric Cancer Who Received Systemic Chemotherapy
by Min-Kyue Shin, Min-Gew Choi, Seung-Tae Kim, Won-Ki Kang, Tae-Sung Sohn, Ji-Yeong An, Joon-Ho Lee and Jeeyun Lee
Biomedicines 2023, 11(11), 3097; https://doi.org/10.3390/biomedicines11113097 - 20 Nov 2023
Cited by 11 | Viewed by 4506
Abstract
With the advances in chemotherapy and immunotherapy, a small subset of patients may be eligible for conversion surgery after achieving tumor regression with chemotherapy. This is a retrospective cohort study of 118 patients with stage IV gastric cancer who received palliative chemotherapy and [...] Read more.
With the advances in chemotherapy and immunotherapy, a small subset of patients may be eligible for conversion surgery after achieving tumor regression with chemotherapy. This is a retrospective cohort study of 118 patients with stage IV gastric cancer who received palliative chemotherapy and conversion surgery with a negative resection margin at Samsung Medical Center. Baseline features included comorbidities, body mass index (BMI), carcinoembryonic antigen (CEA) level, primary tumor size, biopsy histology, distant metastatic sites, and molecular markers—HER2, MSI/MMR, PD-L1, and EBV. Post-chemotherapy features included BMI, CEA level, chemotherapy regimen, objective response to chemotherapy, and number of preoperative chemotherapy cycles. Post-operational features included tumor size, histologic differentiation and Lauren’s classification, pathologic tumor and nodal stages, invasion of lymphatics/vessels/nerves, peritoneal cytology, and the receipt of postoperative chemotherapy. Of 118 patients, 60 patients received total gastrectomy and 58 patients received subtotal gastrectomy. In all, 21 patients achieved a pathologic complete response, and 97 patients achieved downstaging to yp stage I, II, or III. Before conversion surgery, patients received first-line capecitabine/oxaliplatin (62%), HER2 inhibitors combined with chemotherapy (18%), immune checkpoint inhibitors (15%), and inhibitors of MET or VEGFR2 (5%). In the multivariable analysis, BMI at the time of diagnosis, either HER2 positive, high MSI, or deficient MMR, and the use of targeted agents were significant prognostic factors. Conversion surgery could be considered in patients with stage IV gastric cancer regardless of the initial disease burden. BMI and molecular markers are important prognostic factors that can be used to select candidates. Full article
(This article belongs to the Section Cancer Biology and Oncology)
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11 pages, 1544 KB  
Article
Unsolved Issues in Thymic Epithelial Tumour Stage Classification: The Role of Tumour Dimension
by Carolina Sassorossi, Pietro Bertoglio, Filippo Lococo, Gloria Santoro, Elisa Meacci, Dania Nachira, Maria Teresa Congedo, Jury Brandolini, Matteo Petroncini, Adriana Nocera, Diepriye Charles-Davies, Piergiorgio Solli, Stefano Margaritora and Marco Chiappetta
Diagnostics 2023, 13(22), 3468; https://doi.org/10.3390/diagnostics13223468 - 17 Nov 2023
Cited by 4 | Viewed by 1699
Abstract
According to the different classifications now in use, thymic tumours are staged by the extent of local invasiveness, and tumour size is not included as a major determinant for the T category. The aim of this double-site retrospective study is to analyse the [...] Read more.
According to the different classifications now in use, thymic tumours are staged by the extent of local invasiveness, and tumour size is not included as a major determinant for the T category. The aim of this double-site retrospective study is to analyse the correlation between tumour dimension and overall survival (OS) in patients who underwent surgical treatment. From January 2000 to December 2020, patients with thymic epithelial tumours who underwent surgical resection were included in this study. Data from a total of 332 patients were analysed. Five- and ten-year overall survival (5–10 YOS) was 89.26% and 87.08%, respectively, while five- and ten-year disease-free survival (DFS) was 88.12% and 84.2%, respectively. Univariate analysis showed a significant correlation between male sex (p-value 0.02), older age (p-value < 0.01), absence of myasthenia gravis (p-value < 0.01), increase in pTNM (pathological Tumor Node Metastasis) (p-value 0.03) and increase in the number of infiltrated organs (p-value 0.02) with an increase in tumour dimension. Tumour dimension alone was not effective in the prediction of DFS and OS, both when considered as a continuous variable and when considered with a cut-off of 3 and 5 cm. However, with multivariate analysis, it was effective in predicting OS in the aforementioned conditions (p-value < 0.01). Moreover, multivariate analysis was also used in the thymoma and Masaoka I subgroups. In our experience, the role of tumour dimension as a descriptor of the T parameter of the TNM (Tumor Node Metastasis) staging system seemed to be useful in improving this system. Full article
(This article belongs to the Section Pathology and Molecular Diagnostics)
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