Search Results (35)

Background: The incidence of colorectal cancer diagnosed before age 50 has been increasing worldwide. However, limited data describe the endoscopic and pathological features of colorectal lesions encountered and treated during routine colonoscopy in younger adults. This study aimed to characterize age-related differences in endoscopically resected colorectal neoplasia. Methods: We conducted a retrospective, single-center observational study of consecutively endoscopically resected colorectal neoplasia at a high-volume academic teaching hospital in Japan. Patient-level and lesion-level characteristics were compared between early-onset (<50 years) and later-onset (≥50 years) groups. Lesions were evaluated for location, morphology, size, histology, resection method, and advanced neoplasia status. Results: A total of 1299 patients with 3399 lesions were analyzed, including 498 early-onset patients with 940 lesions. Early-onset neoplasia showed a left-sided predominance, with higher proportions in the distal colon and rectum. Pedunculated morphology was more frequently observed in early-onset lesions. Early-onset disease was also associated with larger lesion size, a higher prevalence of high-grade tubular adenoma, and increased rates of advanced adenoma and advanced neoplasia, resulting in more frequent use of endoscopic mucosal resection or submucosal dissection. Conclusions: Endoscopically resected colorectal lesions in younger adults exhibit distinct anatomical and morphological features compared with later-onset cases, indicating heterogeneity at the premalignant stage. Full article

Background: Hypophosphatemia is a frequently underestimated metabolic disorder, yet it can be one of the first biochemical findings in primary hyperparathyroidism (PHPT). Current diagnostic and surgical criteria for PHPT do not include serum phosphate, despite its potential value as an early marker. Methods: We report the case of a 79-year-old woman with type 2 diabetes mellitus, hypertension and osteoarthritis, followed since 2015 for persistent hypophosphatemia (0.8 mg/dL) and stress fractures. Results: Initial calcium and vitamin D levels were normal, but PTH was elevated. Bone scintigraphy revealed multiple stress fractures, while ultrasound and sestamibi scan were inconclusive. Despite cholecalciferol and calcitriol supplementation, hypophosphatemia persisted. From 2023, progressive hypercalcemia developed (10.9 mg/dL), with sustained hypophosphatemia (1.7 mg/dL), persistently high PTH (121 pg/mL) and markedly elevated FGF-23 (1694 kRU/L). Renal phosphate wasting was demonstrated, with reduced tubular reabsorption. An 18F-fluorocholine PET-CT performed in 2024 identified two right parathyroid adenomas, establishing the diagnosis of PHPT. The patient was referred for parathyroidectomy. Conclusions: Hypophosphatemia may serve as a complementary biomarker in the diagnostic and therapeutic approach to PHPT, but only after other potential causes of low phosphate levels have been excluded, as illustrated in this case. Its consideration could facilitate the early identification of PHPT and improve clinical decision-making, particularly in patients who do not meet classical surgical indications. Full article

Background: The pathogenesis of various colon-related pathologies, including irritable bowel syndrome, uncomplicated diverticulitis, and tubular adenoma, remains unknown, primarily due to their multifactorial nature. These gastrointestinal diseases are increasing in prevalence in Western countries and are common conditions worldwide. Objective: To identify intestinal microbiota signs and their associations with the development of colonic pathologies, such as irritable bowel syndrome, uncomplicated diverticulitis, and tubular adenoma. Materials and Methods: An observational, prospective, cross-sectional study was conducted to compare the microbiome among three conditions via 16S rRNA sequencing of biopsy samples obtained via colonoscopy. Results: The microbiome of individuals with tubular adenoma was less diverse than that of patients with diverticulitis and irritable bowel syndrome, with a lower abundance of commensal bacterial genera, such as Catenibacterium, Bifidobacterium, and Faecalibacterium, and an increase in several genera with known pathogenic roles, including Escherichia–Shigella, Fusobacteria, Prevotella, and Haemophilus. No significant association was found between the type of pathology and the total pathogenic or commensal disease score; however, a ratio of 2.54 to pathogenic/commensal was observed in the IBS patient group. In contrast, in the diverticulitis and adenoma patient groups, this ratio was 8. Conclusions: These results provide evidence supporting the proposal that alterations in the colonic microbiome could be involved in various colonic pathogeneses and that an imbalance between commensal and pathogenic populations could be directly related to pathogenesis in the microsystem. It is important to highlight the need for future studies. Full article

Breast cancer is a significant cause of cancer-related mortality among women around the globe, underscoring the need for early and accurate diagnosis. Typically, histopathological analysis of biopsy slides is utilized for tumor classification. However, it is labor-intensive, subjective, and often affected by inter-observer variability. Therefore, this study explores a deep learning-based, multi-class classification framework for distinguishing breast cancer subtypes using convolutional neural networks (CNNs). Unlike previous work using the popular BreaKHis dataset, where binary classification models were applied, in this work, we differentiate eight histopathological subtypes: four benign (adenosis, fibroadenoma, phyllodes tumor, and tubular adenoma) and four malignant (ductal carcinoma, lobular carcinoma, mucinous carcinoma, and papillary carcinoma). This work leverages transfer learning with ImageNet-pretrained ResNet architectures (ResNet-18, ResNet-34, and ResNet-50) and extensive data augmentation to enhance classification accuracy and robustness across magnifications. Among the ResNet models, ResNet-50 achieved the best performance, attaining a maximum accuracy of 92.42%, an AUC-ROC of 99.86%, and an average specificity of 98.61%. These findings validate the combined effectiveness of CNNs and transfer learning in capturing fine-grained histopathological features required for accurate breast cancer subtype classification. Full article

Background and Objectives: Colorectal cancer (CRC) is a major cause of cancer morbidity and mortality worldwide. Genetic and epigenetic changes, especially DNA methylation alterations, are key in CRC development. LINE-1 hypomethylation marks global DNA methylation loss and genomic instability, making it a potential early CRC biomarker. This study investigates the methylation status of LINE-1 in colorectal adenocarcinoma, precancerous lesions (tubular and serrated adenomas), and the surrounding normal mucosa, aiming to elucidate its role as an epigenetic marker in early colorectal tumorigenesis. Materials and Methods: Paired lesion and normal tissue samples from 66 patients were analyzed for LINE-1 methylation at three CpG sites using bisulfite pyrosequencing. Results: Adenocarcinomas and tubular adenomas showed significant hypomethylation, especially at loci A and B, while serrated adenomas exhibited no significant differences. Conclusions: LINE-1 hypomethylation is associated with colorectal tumorigenesis, with distinct patterns observed between tubular and serrated adenomas, indicating distinct pathways forming and progressing specific adenomas. These findings support the potential of LINE-1 methylation as an early epigenetic biomarker for CRC risk stratification and highlight the need for further research into its clinical utility. Full article

Objective: Although prior research developed an artificial intelligence (AI)-based classification system predicting colorectal lesion histology, the heavy computational demands limited its practical application. Recent advancements in medical AI emphasize decentralized architectures using edge computing devices, enhancing accessibility and real-time performance. This study aims to construct and evaluate a deep learning-based colonoscopy image classification model for automatic histologic categorization for real-time use on edge computing hardware. Design: We retrospectively collected 2418 colonoscopic images, subsequently dividing them into training, validation, and internal test datasets at a ratio of 8:1:1. Primary evaluation metrics included (1) classification accuracy across four histologic categories (advanced colorectal cancer, early cancer/high-grade dysplasia, tubular adenoma, and nonneoplasm) and (2) binary classification accuracy differentiating neoplastic from nonneoplastic lesions. Additionally, an external test was conducted using an independent dataset of 269 colonoscopic images. Results: For the internal-test dataset, the model achieved an accuracy of 83.5% (95% confidence interval: 78.8–88.2%) for the four-category classification. In binary classification (neoplasm vs. nonneoplasm), accuracy improved significantly to 94.6% (91.8–97.4%). The external test demonstrated an accuracy of 82.9% (78.4–87.4%) in the four-category task and a notably higher accuracy of 95.5% (93.0–98.0%) for binary classification. The inference speed of lesion classification was notably rapid, ranging from 2–3 ms/frame in GPU mode to 5–6 ms/frame in CPU mode. During real-time colonoscopy examinations, expert endoscopists reported no noticeable latency or interference from AI model integration. Conclusions: This study successfully demonstrates the feasibility of a deep learning-powered colonoscopy image classification system designed for the rapid, real-time histologic categorization of colorectal lesions on edge computing platforms. This study highlights how nature-inspired frameworks can improve the diagnostic capacities of medical AI systems by aligning technological improvements with biomimetic concepts. Full article

Mammary gland tumors in dogs are very common in clinical practice. Betulinic acid is currently a compound considered to have anticancer properties in human mammary tumors via nanoemulsions. In this study, betulinic acid nanoemulsions with a particle size of less than 300 nm were prepared. Biopsies were obtained from five female dogs with mammary tumors for histopathological analysis, confirming that two were tubular mammary carcinomas (MMTs, malignant) and three were complex mammary adenomas (BMTs, benign). The five female dogs were administered with a daily oral dose of nanoemulsion containing 5 mg/kg of betulinic acid for 30 days. Tumor size was measured every 7 days, and the response to treatment was assessed according to RECIST (Response Evaluation Criteria In Solid Tumors) standards. In one of the females with MMTs treated with the nanoemulsion, the tumor size was reduced by approximately 38%, while in the BMT female dogs, the nanoemulsion reduced the tumor size by 25.3%. It was concluded that oral administration of betulinic acid nanoemulsions reduced the size of canine mammary tumors. Experimental studies are still needed to further evaluate this preparation. Full article

Background: Colorectal cancer (CRC) is characterized by the uncontrolled growth of malignant colonic or rectal crypt epithelium. About 85% of CRCs evolve through a stepwise progression from advanced precancerous adenoma lesions. A better understanding of the evolution from adenoma to carcinoma can provide a window of opportunity not only for early detection and therapeutic intervention but potentially also for cancer prevention strategies. Methods: This study investigates the heterogeneous methylation, copy-number alteration (CNA), and mutation signals of histological adenoma subtypes in the context of progression from normal colon to advanced precancerous lesions (APLs) and early-stage CRC. Results: Differential methylation analysis revealed 2321 significantly altered regions among APLs: 137 hypermethylated regions in serrated vs. tubular, 2093 in serrated vs. tubulovillous, and 91 in tubular vs. tubulovillous adenoma subtypes. The most differentiating pathways for serrated adenomas belonged to cAMP signaling and the regulation of pluripotency of stem cells, while regions separating tubular and tubulovillous subtypes were enriched for WNT signaling. CNA events were mostly present in tubular or tubulovillous adenomas, with the most frequent signals being seen in chromosomes 7, 12, 19, and 20. In contrast, early-stage CRC exhibited signals in chromosomes 7, 8, and 20, indicating different processes between APL and early-stage CRC. Mutations reinforce subtype-level differences, showing specific alterations in each subtype. Conclusions: These findings are especially important for developing early detection or cancer prevention tests trying to capture adenoma signatures. Full article

Background: Colorectal cancer (CRC) is the second leading cause of cancer death in Kuwait. The effectiveness of colonoscopy in preventing CRC is dependent on a high adenoma detection rate (ADR). Computer-aided detection can identify (CADe) and characterize polyps in real time and differentiate benign from neoplastic polyps, but its role remains unclear in screening colonoscopy. Methods: This was a randomized-controlled trial (RCT) enrolling patients 45 years of age or older presenting for outpatient screening or surveillance colonoscopy (Kuwait clinical trial registration number 2047/2022). Patients with a history of inflammatory bowel disease, alarm symptoms, familial polyposis syndrome, colon resection, or poor bowel preparation were excluded. Patients were randomly assigned to either high-definition white-light (HD-WL) colonoscopy (standard of care) or HD-WL colonoscopy with the CADe system. The primary outcome was ADR. The secondary outcomes included polyp detection rate (PDR), adenoma per colonoscopy (APC), polyp per colonoscopy (PPC), and accuracy of polyp characterization. Results: From 1 September 2022 to 1 March 2023, 102 patients were included and allocated to either the HD-WL colonoscopy group (n = 51) or CADe group (n = 51). The mean age was 52.8 years (SD 8.2), and males represented 50% of the cohort. Screening for CRC accounted for 94.1% of all examinations, while the remaining patients underwent surveillance colonoscopy. A total of 121 polyps were detected with an average size of 4.18 mm (SD 5.1), the majority being tubular adenomas with low-grade dysplasia (47.1%) and hyperplastic polyps (46.3%). There was no difference in the overall bowel preparation, insertion and withdrawal times, and adverse events between the two arms. ADR (primary outcome) was non-significantly higher in the CADe group compared to the HD colonoscopy group (47.1% vs. 37.3%, p = 0.3). Among the secondary outcomes, PDR (78.4% vs. 56.8%, p = 0.02) and PPC (1.35 vs. 0.96, p = 0.04) were significantly higher in the CADe group, but APC was not (0.75 vs. 0.51, p = 0.09). Accuracy in characterizing polyp histology was similar in both groups. Conclusions: In this RCT, the artificial intelligence system showed a non-significant trend towards improving ADR among Kuwaiti patients undergoing screening or surveillance colonoscopy compared to HD-WL colonoscopy alone, while it significantly improved the detection of diminutive polyps. A larger multicenter study is required to detect the true effect of CADe on the detection of adenomas. Full article

Background: The colorectal adenoma undergoes neoplastic progression via the normal epithelium–adenoma–adenocarcinoma sequence as reported in the Vogelgram. The hazard of developing a tumor is deeply associated with the number and size of adenomas and their subtype. Adenomatous polyps are histologically categorized as follows: approximately 80–90% are tubular, 5–15% are villous, and 5–10% are tubular/villous. Given the higher risk of a malignant transformation observed in tubular/villous adenomas, patients diagnosed with adenomatous polyposis are at an improved risk of developing CRC. The Wnt/β-catenin pathway plays a key role in the onset of colorectal adenoma; in particular, intestinal cells first acquire loss-of-function mutations in the APC gene that induce the formation of adenomas. Methods: Wnt/β-catenin pathway APC, Wnt3a, Wnt5a, LEF1, and BCL9 genes and protein expression analyses were conducted by qRT-PCR and western blot in 68 colonic samples (polyps and adjacent mucosa) from 41 patients, of which 17 were affected by FAP. Ten normal colonic mucosal samples were collected from 10 healthy donors. Results: In this study, both the APC gene and protein were less expressed in the colon tumor compared to the adjacent colonic mucosa. Conversely, the activated β-catenin was more expressed in polyps than in the adjacent mucosa. All results confirmed the literature data on carcinomas. A statistically significant correlation between Wnt3a and BCL9 both in polyps and in the adjacent mucosa underlines that the canonical Wnt pathway is activated in early colon carcinogenesis and that the adjacent mucosa is already altered. Conclusion: This is the first study analyzing the difference in expression of the Wnt/β-catenin pathway in human colorectal adenomas. Understanding the progression from adenomas to colorectal carcinomas is essential for the development of new therapeutic strategies and improving clinical outcomes with the use of APC and β-catenin as biomarkers. Full article

Compared to the number of studies on the neoplasms of laboratory rodents, fewer studies have focused on spontaneous neoplasms in pet rodents. Notably, the mouse mammary tumor virus (MMTV) is associated with mammary tumors in rodents. In this study, 77 tumors and tumor-like lesions of biopsy samples were collected from 70 pet rodents, including hamsters (n = 47), guinea pigs (n = 16), unknown species (n = 4), rats (n = 2), and a gerbil. Fifty tumors were collected from 47 hamsters, in which the most common tumors were mammary tumors (13/50), followed by fibrosarcoma (9/50), mast cell tumors (4/50), and squamous cell carcinoma (4/50). The collected subtypes of mammary tumors in hamsters included tubular carcinoma (n = 5), tubular adenoma (n = 4), carcinoma and malignant myoepithelioma (n = 1), simple tubular carcinoma (n = 1), adenosquamous carcinoma (n = 1), and tubulopapillary adenoma (n = 1). In addition, twenty tumors were collected from guinea pigs, in which the most common tumor was lipoma (6/20), followed by adenocarcinoma of the mammary gland (4/20), trichofolliculoma (2/20), and collagenous hamartomas (2/20). In guinea pigs, the subtypes of mammary gland tumors were tubular carcinoma (n = 2), tubular and solid carcinoma (n = 1), and tubulopapillary carcinoma (n = 1). In 20 cases of mammary tumors, MMTV was not detected, implicating no evidence of MMTV infection in mammary oncogenesis in pet rodents in Taiwan. Full article

(1) Background: Parathyroid cystic adenomas (PCA) are rare entities representing only 0.5–1% of parathyroid adenomas, accounting for 1–2% of cases of primary hyperparathyroidism (PHPT). The purpose of this study was to compare classical and functional/secreting cystic parathyroid lesions and identify risk factors for severe hypercalcemia; (2) Methods: A total of 17 patients with PHPT and parathyroid cysts (study group) were compared with the group of 100 patients with hyperparathyroidism caused by adenoma or hyperplasia (control group). In both groups the majority were women (88% vs. 12%, with gender ratio 7, 3:1). The patients were examined preoperatively and postoperatively: PTH, creatine, calcium and phosphate serum and urine concentrations and calcidiol serum levels were assessed; (3) Results: Patients with parathyroid cyst had statistically higher PTH and calcium serum concentration, higher calciuria and lower serum phosphate concentration. There were no statistically significant differences in the concentration of creatine in serum and urine and tubular reabsorption of phosphorus (TRP); (4) Conclusions: Due to higher PTH and calcium levels, cystic parathyroid adenomas could be one of the rare risk factors for severe hypercalcemia and hypercalcemic crisis which can be life threatening. Full article

Background: Sessile serrated adenomas are important precursors to colorectal cancers and account for 30% of colorectal cancers. The United States Multi-Society Task Force recommends that patients with sessile serrated adenomas undergo surveillance similar to tubular adenomas. However, the risk of metachronous neoplasia when the high-risk adenoma co-exists with sessile serrated adenomas is poorly defined. Objective: To examine the risk of metachronous neoplasia in the presence of high-risk adenoma and synchronous sessile serrated adenomas compared with isolated high-risk adenoma. Data sources: PubMed, Embase, Scopus, Cochrane Library. Study selection: A literature search for studies evaluating the risk of metachronous neoplasia in patients with high-risk adenoma alone and those with synchronous high-risk adenoma and sessile serrated adenomas during surveillance colonoscopy was conducted on online databases. Main outcome measures: The primary outcome of interest was the presence of metachronous neoplasia. Results: Of the 1164 records reviewed, six (four retrospective and two prospective) studies met inclusion criteria with 2490 patients (1607 males, mean age 59.98 ± 3.23 years). Average follow-up was 47.5 ± 12.5 months. There were 2068 patients with high-risk adenoma on index colonoscopy and 422 patients with high-risk adenoma and synchronous sessile serrated adenomas. Pooled estimates showed a significantly elevated risk for metachronous neoplasia in patients with high-risk adenoma and synchronous sessile serrated adenomas (pooled odds ratio 2.21; 95% confidence intervals 1.65–2.96; p < 0.01). There was low heterogeneity (I² = 11%) among the studies. Sensitivity analysis of the prospective studies alone also showed elevated risk of metachronous neoplasm (pooled odds ratio 2.56; 95%, confidence intervals 1.05–6.23; p = 0.04). Limitations: Inclusion of a small number of retrospective studies. Conclusions: The presence of high-risk adenomas and synchronous sessile serrated adenomas is associated with an increased risk of metachronous neoplasia. Therefore, shorter surveillance intervals may be considered in patients with high-risk adenoma and synchronous sessile serrated adenomas compared to those with high-risk adenoma alone. Full article

The preventive efficacy of MUC1-specific DNA immunization on inflammation-driven colon carcinogenesis in human MUC1 transgenic (MUC1.Tg) mice was investigated. Mice were vaccinated with MUC1 DNA mixed with autologous bone-marrow-derived dendritic cells (BMDCs), and then colonic tumors were induced by azoxymethane (AOM) injection and oral administration of dextran sulfate sodium (DSS). Two types of tumors, squamous metaplasia and tubular adenoma, were observed. Both expressed high levels of MUC1 as indicated by the binding of anti-MUC1 antibodies with different specificities, whereas MUC1 expression was not detected in normal colonic mucosa. When mice were immunized with MUC1 DNA + BMDCs, tumor incidence, tumor number, and tumor size were significantly reduced. In contrast, vaccination with MUC1 DNA alone or BMDCs alone was ineffective in reducing tumor burden. Inflammation caused by DSS was not suppressed by the MUC1 DNA + BMDCs vaccination. Furthermore, MUC1 protein expression levels, as judged by anti-MUC1 antibody binding in tumors grown after vaccination, did not significantly differ from the control. In conclusion, an inflammation-driven carcinogenesis model was established in MUC1.Tg mice, closely resembling human colon carcinogenesis. In this model, vaccination with MUC1 DNA + BMDCs was effective in overriding MUC1 tolerance and reducing the tumor burden by a mechanism not affecting the level of colonic inflammation. Full article

Sporadic colorectal cancer arises from an adenoma. As mutations in the adenomatous polyposis coli (APC) tumor suppressor gene have been frequently detected in colorectal adenomas, the APC gene is considered a gatekeeper in colorectal carcinogenesis. Here, we report a case of sporadic multiple colonic adenomas that were accompanied by an APC-truncating mutation. A 25-year-old Korean woman presented with dozens of incidentally found colonic polyps. There was no family history of colorectal polyposis or colon cancer in her first or second-degree relatives. All the polyps were removed endoscopically at once, and their pathological examination revealed tubular adenoma. Mutational analysis showed a 2-bp deletion mutation at codon 443, which generates a premature stop codon at codon 461 of the APC gene, and Western blot analysis demonstrated both wild-type and truncated APC proteins in adenoma tissue. This study suggests that a single truncating mutation of the APC gene may initiate adenoma formation. Full article