Invasive lobular breast carcinoma is characterized by infiltrative growth and a tendency toward atypical metastasis, including to the gastrointestinal tract, where metastases are often diffusely infiltrative, complicating their visualization and potentially leading to diagnostic errors. This paper presents a clinical case of a 55-year-old female patient with long-standing (approximately 20 years) abdominal pain syndrome. Based on imaging studies and elevated fecal calprotectin levels, this pain syndrome was interpreted as Crohn's disease, despite the lack of response to standard therapy. One year after confirmation of invasive lobular breast cancer (luminal A subtype, T1N1M0), the patient continued to experience abdominal symptoms until the development of dynamic intestinal obstruction, which required surgical intervention. Histological and immunohistochemical examination of the resected intestinal segment confirmed metastatic involvement of the small and large intestines. This case demonstrates a rare variant of lobular breast cancer metastasis to the intestine, which had been masquerading as Crohn's disease for a long time. It highlights the need for oncological vigilance in patients with abdominal symptoms and a history of cancer, as well as the crucial role of immunohistochemistry in verifying the diagnosis.

Colorectal cancer (CRC) is a major global health burden, whereas small intestinal cancers are rare despite arising within the same gastrointestinal tract. This disparity suggests that segment-specific epithelial programmes may influence carcinogenesis. NLRP6 is an inflammasome-forming sensor with established roles in epithelial homeostasis, barrier maintenance, mucosal immune surveillance, and host-microbiota interactions. Public human tissue resources, an exploratory reanalysis of currently available single-cell data, and our local colonic cohort, provide hypothesis-generating observations compatible with segmental differences in NLRP6 expression, including very low bulk transcript abundance in human colonic samples. However, the currently available human evidence remains limited and heterogeneous, and does not yet support a simple binary model of presence in the small intestine and absence from the colon. Murine studies nevertheless support biological plausibility, as Nlrp6 deficiency exacerbates inflammation-driven colonic tumourigenesis and impairs epithelial repair. In addition, independent human studies indicate protein-level and clinicopathological relevance of NLRP6 in colonic disease, suggesting that its expression may vary according to segment, cell type, inflammatory context, and disease state. We therefore propose that NLRP6 may function as one candidate component of a segment-restricted epithelial defence and mucosal immune surveillance network in the human gut, potentially shaping CRC-relevant inflammatory and barrier conditions rather than acting as an established human tumour-suppressive mechanism. This model should now be tested through orthogonal human validation, including protein-based assays, spatial and single-cell analyses, and correlation with inflammatory status and clinical outcome, before any biomarker-guided intervention strategies are considered.

Cancer cachexia is frequently associated with altered pharmacokinetics and increased chemotherapy toxicity due to the downregulation of cytochrome P450 (CYP) enzymes. However, the molecular mechanisms driving this broad metabolic suppression remain poorly understood. This study investigated whether tumor-derived parathyroid hormone-related protein (PTHrP) is associated with, and may contribute to, suppression of multiple CYP families. In a rat cachexia model, protein expression of CYP3A, CYP1A, CYP2C, CYP2D, and CYP2E1 was significantly downregulated in both the liver and small intestine. Consistent with these changes, pharmacokinetic analyses using a CYP substrate cocktail demonstrated markedly increased AUC and reduced clearance for probe drugs. In vitro experiments showed that PTHrP treatment reduced these CYP isoforms in primary rat hepatocytes. In human data sets, analysis of The Cancer Genome Atlas (TCGA) hepatocellular carcinoma (HCC) data set revealed a significant negative correlation between PTHrP and CYP gene expression, together with enrichment of NF-κB-related transcriptional programs. Furthermore, multimodal analysis using single-cell RNA sequencing and spatial transcriptomics demonstrated that PTHrP-high tumor regions exhibit suppressed xenobiotic metabolism. Additionally, in breast cancer liver metastases, high tumor PTHrP expression correlated with reduced CYP expression in surrounding nontumor hepatocytes, consistent with a possible paracrine relationship. Collectively, these results support an association between tumor-derived PTHrP and suppression of drug-metabolizing programs. They further suggest that PTHrP may be one contributing factor, but not definitive proof of a principal suppressor, and should therefore be considered a candidate biomarker requiring further mechanistic and clinical validation.

Gastrointestinal cancers encompass a range of malignancies, including esophageal, gastric, esophagogastric, hepatocellular, pancreatic, and intestinal cancers. Considering the prevalence of these cancers, alongside their fatal nature, and the nonspecific symptoms that often arise in the advanced stages, developing a non-invasive screening/diagnostic method capable of detecting cancer early is in high demand. Exhaled breath serves as an accessible source of biomarkers, including volatile organic compounds (VOCs), a promising type of diagnostic marker. This method requires a sample as small as five breaths. Exhaled breath analysis is conducted using different mass spectrometry methods coupled with nano sensors or neural networks. Furthermore, innovative devices like electronic noses have also shown great promise in diagnosing different types of cancers. These biomarkers show potential in reliably differentiating between healthy individuals and cancer patients. Additionally, these compounds can be utilized for cancer staging and monitoring treatment response. However, certain fallbacks persist in differentiating malignant from pre-malignant conditions. Despite the promise of this diagnostic approach, certain limitations, such as variations in VOC profiles across different populations, lack of standardized collection protocols, and absence of established universal reference standards, underscore the need for proper standardization and large-scale, multi-center validation studies.

Carcinoid heart disease (CHD) is a serious cardiac manifestation of carcinoid syndrome (CS), characterized by progressive fibrotic degeneration of cardiac valves and right-sided heart failure. We report the case of a 72-year-old man with a history of metastatic small-intestinal neuroendocrine tumor and CS diagnosed four years earlier, who presented with worsening dyspnea and peripheral edema. Transthoracic echocardiography revealed characteristic findings of advanced CHD, including severely thickened, retracted, and immobile tricuspid and pulmonary valve leaflets, resulting in severe tricuspid and pulmonary regurgitation. Additional findings included right ventricular dilatation, severe biatrial enlargement, moderate mitral regurgitation, a small pericardial effusion, and a 7-cm ascending aortic aneurysm. The diagnosis was established based on the characteristic echocardiographic appearance and elevated N-terminal pro-B-type natriuretic peptide levels. Notably, no routine cardiological surveillance had been performed following the diagnosis of CS. The patient was managed conservatively with intravenous diuretic therapy and optimization of heart failure treatment. Following multidisciplinary evaluation, surgical intervention was not pursued because of the patient's advanced disease stage, clinical instability, and concomitant ascending aortic aneurysm, which collectively rendered him a prohibitive surgical candidate. His clinical course was subsequently complicated by acute kidney injury with progressive renal dysfunction and anuria, and he ultimately died during hospitalization. This case highlights the importance of regular cardiovascular follow-up in patients with CS, as delayed recognition of cardiac involvement may lead to advanced and potentially irreversible valvular disease. Early detection remains crucial for timely intervention and may improve clinical outcomes.

Cancer remains a major global health challenge, with its growing incidence highlighting the critical need for effective and accessible treatments. Current therapeutic approaches, including surgery, chemotherapy, radiation therapy, hormone therapy, and immuno-therapy, are often limited by toxicity, poor targeting, and suboptimal efficacy. These challenges have driven the development of nanotechnology-based strategies aimed at improving tumor selectivity and therapeutic outcomes. Among the most promising are extracellular vesicles, particularly exosomes (30-150 nm), which have garnered significant attention as natural nanocarriers due to their inherent role in intercellular communication and their capacity to encapsulate proteins, nucleic acids, and lipids. Exosomes can be obtained from a wide range of sources, including biological fluids, cell cultures, and unconventional origins such as plants and microorganisms. Of particular interest are milk- and colostrum-derived exosomes, particularly those of bovine origin, have emerged as a promising delivery platform owing to their scalability, biocompatibility, cost-effectiveness and suitability for oral administration. These vesicles possess immunomodulatory properties, demonstrate stability under gastrointestinal conditions, and are readily internalized by intestinal epithelial cells. Furthermore, surface engineering with targeting ligands such as folic acid can enhance tumor specific delivery by exploiting receptor overexpression while minimizing systemic toxicity. This review critically examines exosome sources, isolation and characterization methodologies, cargo-loading strategies, biodistribution, pharmacokinetics, and engineering approaches together with their applications in delivering small-molecule drugs and nucleic acid-based therapeutics to overcome multidrug resistance in cancer. In addition, current challenges related to exosome heterogeneity, manufacturing, quality control, clinical translation, and regulatory considerations are discussed, together with future perspectives for the development of exosome-based therapeutics.

Enteric duplication cysts (EDCs) are rare congenital abnormalities of the digestive tract. They may occur with different clinical presentations-including acute intestinal obstruction, perforation or bleeding. The aim of this educational case report is to present the diagnostic and therapeutic process of a young male patient admitted for intestinal bleeding. The peculiarity of this case lies in the association between a rare pathology, EDC, and an equally unusual anatomical condition such as intestinal malrotation. A 27-year-old Italian Caucasian man was admitted with diarrhea and currant jelly stool. No gastrointestinal disorders or previous history of bleeding or chronic abdominal pain were reported. He denied habitual use of nonsteroidal anti-inflammatory drugs (NSAIDs), or other enterotoxic drugs. A small bowel CT scan showed a suspected acute enteritis. A more careful analysis revealed radiological signs of intestinal malrotation. An endoscopic video-capsule could not clearly identify the source of bleeding. The device-assisted enteroscopy revealed, at the mid-distal jejunal level, a double intestinal lumen with traces of digested blood material. The patient successfully underwent a surgical definitive treatment of the jejunal duplication cyst, and was soon discharged. The combination of multiple diagnostic tools, both radiological and endoscopic (entero-CT scan, small bowel video-capsule, and finally device-assisted enteroscopy), allowed for a multidisciplinary approach that led to the diagnosis of a rare small intestinal duplication cyst in a young male patient with congenital intestinal malrotation.

Brunner's gland hyperplasia (BGH) is an uncommon benign proliferative condition of the Brunner's glands. It is often asymptomatic and typically discovered incidentally during endoscopic procedures. We report a case of a patient with BGH diagnosed with endoscopic ultrasound biopsy after an initial negative endoscopic mucosal biopsy. A 52-year-old male presented with palpitations and exertional dyspnea as well as melenic stools of a 3-week duration. Laboratory testing was remarkable for a hemoglobin level of 5.9 g/dl and a mean corpuscular volume of 62 fl. Esophagogastroduodenoscopy and mucosal biopsy were inconclusive, necessitating endoscopic ultrasound with fine-needle biopsies. Due to bleeding, the mass was resected, and histological examination revealed the diagnosis of BGH. This case underscores the importance of considering BGH in the differential diagnosis of gastrointestinal bleeding.

Nucleoporins (NUPs) constitute the nuclear pore complex (NPC) and are essentially involved in nuclear transport, chromatin organization, and context-dependent gene regulation. However, the role of NUPs in neuroendocrine (tumor)biology and related diagnostic potential is poorly defined. In this study, we comparatively analyzed immunohistochemical expression patterns of NUP98 and NUP153 (sharing structural and functional similarities) across a large variety of human tissues and tumors (total N > 600), with a focus on neuroendocrine neoplasms (NENs (n = 361)). While both NUPs showed a nuclear rim accentuated staining pattern, NUP98 exhibited ubiquitous and NUP153 a striking cell- and tissue/tumor-type-dependent immunoreactivity. More specifically, NUP153 immunoreactivity was consistently detectable in neuroendocrine tissues (e.g., pancreatic islets) and retained in neuroendocrine tumors (NETs) of the pancreas, lung, appendix, and small intestine, but almost completely absent in neuroendocrine carcinomas (NECs) and non-neuroendocrine carcinomas. Loss of NUP153 staining correlated with poorer clinical outcomes in pancreatic NETs. Further analyses revealed that NUP153 messenger ribonucleic acid (mRNA) and total protein levels were not significantly different between NETs and non-neuroendocrine carcinomas, as evaluated by quantitative real-time polymerase chain reaction and targeted proteomics. Differential isoform usage was ruled out by polymerase chain reaction and sequencing as another possible explanation for the discriminative immunohistochemical findings. Finally, a high density of post-translational modifications (PTMs) within the antigen sequence could be discovered and indicated PTM-dependent detection as the likely cause of differential staining. Collectively, our findings suggest that NUP153 is a differentiation-dependent and PTM-sensitive immunohistochemical marker in NENs with diagnostic and prognostic potential. It also emphasizes the importance of orthogonal molecular analyses for correct interpretation of IHC stainings.