Primary cutaneous cribriform tumor is a rare sweat gland neoplasm with a characteristic histologic architecture and typically benign clinical behavior. We present the first reported pediatric case in a 10-year-old female who developed a painful, firm nodular lesion on the lateral aspect of her right foot. Initially thought to be a verruca, the lesion was treated conservatively. However, the persistence of pain prompted a biopsy that revealed features consistent with a primary cutaneous cribriform tumor. Imaging showed no evidence of spread, and the lesion was excised with a conservative surgical approach.

Symptomatic cholelithiasis is the leading indication for pediatric cholecystectomy. While historically linked to hemolytic disorders, non-hemolytic gallbladder disease in children has become increasingly common in recent decades.

The objective of this study was to describe the distribution and temporal trends of indications for cholecystectomy among children (ages ≤ 19 years) undergoing surgery at a tertiary pediatric center in Israel and to compare clinical presentation between hemolysis-related and non-hemolysis-related cases.

We conducted a retrospective observational cohort study of all pediatric patients who underwent cholecystectomy at Schneider Children's Medical Center between 2011 and 2024. Patients with congenital biliary tract anomalies or biliary tract neoplasms were excluded.

A total of 199 cholecystectomies were performed (median age 13.4 years). Hemolysis-related cholelithiasis accounted for 34.2% of cases; five patients (2.5%) had gallbladder polyps or other benign lesions, while the remaining patients had non-hemolysis-related cholelithiasis. No cases of biliary dyskinesia were identified. The proportion of non-hemolysis-related cholecystectomies remained stable over time. Among symptomatic patients, the rate of choledocholithiasis was significantly higher in the hemolysis-related group compared to the non-hemolysis group (27% vs. 7.9%, p = 0.004). No statistically significant association was observed between obesity and increased disease severity or adverse outcomes.

Unlike trends reported in some Western countries, the number of cholecystectomies performed for non-hemolysis-related cholelithiasis in our single-center cohort did not increase over time. Hemolysis-related disease remains a leading indication for pediatric cholecystectomy. Prophylactic surgery may help prevent biliary complications in this group while symptomatic patients have substantial complication rates.

Sulfated polysaccharides (SPs), biologically active macromolecules from marine and terrestrial organisms, hold significant potential in revolutionizing cancer therapy. Characterized by their unique sulfate ester groups and structural diversity, SPs exhibit a broad spectrum of bioactivities, including immunomodulation, apoptosis induction, metastasis suppression, and angiogenesis inhibition. Prominent SPs, such as fucoidan from brown algae and carrageenan from red algae, have shown remarkable anticancer properties, either as standalone agents or in synergy with conventional therapies like chemotherapy and radiotherapy. Their mechanisms of action involve targeting critical pathways such as NF-kB, VEGF, and PI3K/Akt, disrupting cancer cell proliferation, invasion, and tumor microenvironment dynamics. SPs also enhance immune system responses, reduce chemotherapy-induced side effects, and exhibit antioxidant properties, making them versatile candidates in cancer treatment. Innovations like SP-based nanoparticles are addressing bioavailability and drug delivery challenges, providing targeted and sustained therapeutic effects while minimizing off-target toxicity. Despite their promise, challenges such as structural complexity, scalability, and clinical validation hinder their widespread adoption. This review provides a comprehensive analysis of SPs' therapeutic potential, mechanisms, and emerging applications in oncology. It emphasizes the need for advanced extraction, characterization techniques, and clinical research to unlock their full potential, paving the way for novel, efficient, and safer cancer therapies.

Tumor metastasis is closely associated with coagulation and inflammation, particularly via thrombin-PAR1 signaling. However, the potential of natural polysaccharides such as rhamnan sulfate (RS) to modulate these pathways and suppress metastasis remains unclear. We aimed to investigate the effects of orally administered RS derived from Monostroma nitidum on melanoma metastasis and its underlying mechanisms. Male C57BL/6J mice were orally administered water or RS daily. On day 8, saline or B16 melanoma cells were injected intravenously. Mice were treated for 21 days and divided into four groups (control, RS-only, M + W, and M + RS; n = 5/group). Metastasis and related molecular factors were analyzed in plasma, lung, and aortic tissues. Significant lung and aortic metastases were observed in the M + W group but were markedly suppressed in the M + RS group. RS reduced the expression of inflammatory factors (e.g., IL-6, PAR1), proteases, leukocyte activation markers, complement factors, angiogenic factors, and EMT-related factors. Conversely, thrombin, thrombomodulin, plasmin, TAFIa, and tight junction proteins were increased in RS-treated mice. RS suppresses melanoma metastasis by modulating thrombin-PAR1-mediated inflammation and associated pathways. These findings suggest RS as a potential therapeutic agent, although further mechanistic and clinical studies are required.

In this study, we explore the molecular basis of the literature-reported inverse association between brain neoplasms and neurodegenerative disorders, including Parkinson's disease (PD). As miRNAs are post-transcriptional regulators, we selected them as candidates underlying opposite processes of neurodegeneration and glioma development.

We used bioinformatic analyses for disease-gene extraction, miRNA target prediction, enrichment analyses, and miRNA ranking. We identified 953 shared genes between PD and glioblastoma (GBM) in DisGeNET, then prioritized miRNAs predicted to regulate the largest number of shared targets. Next, we collected peripheral blood from patients with PD (n = 12), patients with gliomas (the most advanced-grade IV, n = 10 and grade III n = 3) and controls undergoing spinal surgery for disk pathology (n = 10). Blood samples were obtained pre-operatively in controls and glioma patients. Tumor and peritumoral tissues were obtained from glioma patients, whereas tissue sampling is not feasible in PD. Brain tissues and plasma were analyzed using RT-qPCR (miRNA) and ELISA (p53).

We observed increased levels of miR-16-5p (p < 0.05) and p53 protein (p < 0.05) in tumor tissues compared with peritumoral tissue. Additionally, miR-16-5p and miR-32-5p plasma levels were elevated in glioma patients compared with both PD patients (p < 0.01 and p < 0.001, respectively) and controls (p < 0.01 and p < 0.001, respectively). Plasma levels in PD did not differ from controls.

Although these analyses highlight miR-16-5p and miR-32-5p as candidate biomarkers associated with glioma related pathways, the results did not provide evidence for the expected opposite regulation between PD and glioma. Future studies with a larger cohort of patients using high-throughput methods are needed to validate these findings and to elucidate the mechanisms driving neurodegeneration or excessive proliferation.

The advent of immune checkpoint inhibitors has driven progress in hepatocellular carcinoma (HCC) treatment outcomes and enabled opportunities for combining therapeutic modalities. Growing evidence substantiates the utility of radiotherapy, particularly at ablative doses, in the management of HCC. Given the potential for radiotherapy to induce an immunostimulatory environment and potentiate immune checkpoint inhibitor activity, the expanding HCC treatment landscape compels exploration of the combination of radiotherapy and immunotherapy. This review highlights recent advances in the treatment of HCC using radiotherapy and immunotherapy in combination. Radiation can potentiate an anti-tumor response and tumor microenvironment permissive to immunotherapy. Results from randomized clinical trials and retrospective studies consistently show that combinations of radiotherapy and immunotherapy improved the treatment outcomes of unresectable or advanced HCC-especially HCC with macrovascular invasion. Active research to further improve treatment efficacy and reduce side effects is exemplified by more than 20 ongoing clinical trials combining external beam radiotherapy and immunotherapy to treat HCC. Ongoing research aims at prolonging survival and downstaging advanced or unresectable HCC.

Colorectal cancer (CRC) remains one of the most prevalent malignancies worldwide and is the second largest contributor to both incidence and mortality, underscoring the urgent need for effective prevention strategies. This comprehensive review provides the most up-to-date evidence on the protective role of plant-based dietary patterns against CRC carcinogenesis, with particular emphasis on underlying cellular and molecular level mechanisms. Accumulating research demonstrates that plant-based foods, rich in dietary fibre, polyphenols, and multiple other bioactive compounds, promote gut microbial eubiosis, support immune regulation, and modulate adipose tissue homeostasis. These effects are accompanied by intestinal barrier integrity, enhanced production of short-chain fatty acids, and the induction of apoptosis in malignant cells. Moreover, plant-derived nutrients reduce the abundance of pro-inflammatory microbial taxa, decrease oxidative, nitrosative and carbonyl stress, and downregulate pro-inflammatory cytokines and signalling pathways, implicated in tumourigenesis. As a result, plant-based dietary patterns have high potential to reduce CRC risk through modulating the intricate interplay between epigenetics, inflammation, immune dysregulation, metabolic and hormonal disruptions, and gut microbiota, suggesting a highly promising, cost-effective and equitable strategy for CRC prevention.

Background: POLE-mutated endometrial carcinomas are associated with exceptionally favorable outcomes, forming the basis for treatment de-escalation in early-stage disease. Nevertheless, rare adverse clinical courses have been reported. This study describes an unusual case of late metastatic recurrence in a POLE-mutated tumor and provides a review of similar cases in the literature. Methods: We present a detailed clinical, radiological, pathological, and molecular description of a patient who developed metastatic recurrence 16 years after initial surgery. A systematic literature search was conducted to identify reports of recurrence, progression, or cancer-related death in POLE-mutated endometrial carcinoma, with extraction of recurrence patterns, genomic features, treatment, and outcomes. Results: The patient experienced sequential pulmonary, cerebral, and leptomeningeal metastases despite harboring a canonical POLE hotspot mutation, proficient mismatch repair status, wild-type TP53, no additional known driver mutation beyond PTEN alterations. The literature review identified a small number of similarly adverse cases. Reported recurrences were heterogeneous, though distant and occasionally central nervous system involvement were noted. Conclusions: While POLE-mutated tumors overall retain an excellent prognosis, rare cases may follow an atypical and aggressive course. Improved molecular annotation and integrated risk-stratification models are needed to better identify this minority of higher-risk patients.

Epidermal growth factor receptor (EGFR)-kinase domain duplication (KDD) represents an atypical mutation distinct from classical EGFR mutations in lung adenocarcinoma (LUAD). Although first- and second-generation EGFR-tyrosine kinase inhibitors (TKIs) have demonstrated clinical activity in EGFR-KDD, the mechanisms of acquired resistance in this setting remain poorly characterized. Herein, we present a LUAD patient with EGFR-KDD who achieved a sustained initial response to afatinib lasting 67 months before developing acquired resistance. Re-biopsy with next-generation sequencing (NGS) uncovered EGFR T790M, accompanied by EGFR amplification and EGFR M766T. The patient was switched to firmonertinib, with subsequent tumor regression. We reviewed published EGFR-KDD cases that had both acquired resistance to first- or second-generation EGFR-TKIs and corresponding repeat biopsy findings. Five of the eleven cases harbored EGFR T790M, yielding a prevalence of 45%, which is similar to that seen in classical EGFR mutations. This case suggests that EGFR T790M mediates acquired resistance to first- and second-generation EGFR-TKIs in EGFR-KDD, mirroring the resistance pattern observed in classical EGFR mutations.

Microsatellite instability (MSI) testing is frequently used to screen patients for the early detection of Lynch syndrome, the most common hereditary colorectal cancer syndrome. MSI testing compares microsatellite repeat lengths in tumor DNA with those in matched normal tissue from the same patient. Therefore, precise sample identification is critical for obtaining reliable test results. The Penta-C and Penta-D pentanucleotide markers are widely used for sample identification in MSI testing. We investigated instability, defined as allelic mismatches or shifts, discordant fragment sizes, or the appearance of alleles in tumor DNA that were absent in the corresponding normal DNA, in the Penta-C and Penta-D loci across 2609 paired colorectal tumor and matched normal tissue or blood DNA samples. The allele sizes of both markers did not match in 0.3% of microsatellite-stable (MSS) and 12.3% of microsatellite instability-high (MSI-H) patients (p < 0.001, difference in proportions, 12.0% (95% CI, 8.9-15.1%)). Non-matching allele sizes in 12.3% of the MSI-H tumors suggest that other repeat markers may also be unstable and not suitable for sample identification in these tumors.