Search Results (887)

Bladder cancer pathogenesis is closely linked to epigenetic alterations, particularly DNA methylation and demethylation processes. Environmental carcinogens and persistent inflammatory stimuli—such as recurrent urinary tract infections—can induce aberrant DNA methylation, altering gene expression profiles and contributing to malignant transformation. This review synthesizes current evidence on the role of DNA methyltransferases (DNMT1, DNMT3a, DNMT3b) and the hypermethylation of key tumour suppressor genes, including A2BP1, NPTX2, SOX11, PENK, NKX6-2, DBC1, MYO3A, and CA10, in bladder cancer. It also evaluates the therapeutic application of DNA-demethylating agents such as 5-azacytidine and highlights the impact of chronic inflammation on epigenetic regulation. Promoter hypermethylation of tumour suppressor genes leads to transcriptional silencing and unchecked cell proliferation. Urine-based DNA methylation assays provide a sensitive and specific method for non-invasive early detection, with single-target approaches offering high diagnostic precision. Animal models are increasingly employed to validate these findings, allowing the study of methylation dynamics and gene–environment interactions in vivo. DNA methylation represents a key epigenetic mechanism in bladder cancer, with significant diagnostic, prognostic, and therapeutic implications. Integration of human and experimental data supports the use of methylation-based biomarkers for early detection and targeted treatment, paving the way for personalized approaches in bladder cancer management. Full article

Background and Objectives: Acute metastatic cord compression (AMSCC) and femoral impending/pathological fracture negatively impact a patient’s quality of life, morbidity and survival, and are considered significant life events. This study aims to compare AMSCC and FMD as distinct yet overlapping metastatic orthopedic emergencies, addressing whether they represent sequential disease stages or distinct patient subpopulations—an analysis critical for prognosis and treatment planning. Materials and Methods: Records of all patients who underwent surgery for a femoral metastatic disease (FMD) over a decade (2004–2015) and patients who were treated for acute metastatic spinal compression (AMSCC) (2007–2017) were retrieved. There were no patients lost to follow-up. Results: The treatment cohorts were similar in terms of age, gender, tumour origin, and the number of spinal metastases. Fifty-four patients were diagnosed with AMSCC. Following treatment, the Frankel muscle grading improved by 0.5 ± 0.8 grades. Two hundred and eighteen patients underwent surgical intervention for FMD. Seventy percent of femoral metastases were located in the femoral neck and trochanteric area. Impending fractures accounted for 52% of the cohort. The FMD cohort, including impending and pathological fractures, was similar to the AMSCC cohort in terms of age and the time interval between cancer diagnosis and surgery (56.7 ± 74.2 vs. 51.6 ± 69.6, respectively, p = 0.646). The Karnofsky functional score was higher for the FMD cohort (63.3 ± 16.2) than for the AMSCC cohort (48.5 ± 19.5; p < 0.001). The mean survival time for the FMD cohort was double that of the AMSCC, at 18.4 ± 23.5 months versus 9.1 ± 13.6 months, respectively (p = 0.006). Conclusions: In conclusion, this study is novel in proposing that FMD and AMSCC are distinct clinical entities, differing in their impact on patient function and, most importantly, on patient survival. Full article

Background/Objective: One third of “non-functioning adrenal tumours” (NFAs) have mild autonomous cortisol secretion (MACS). An updated analysis of the hormonal biomarkers profile, including risk factors and the rate of post-surgery adrenal insufficiency (PSAI), the duration of restoring the normal adrenocortical function in MACS/NFA and potential impacts on clinical comorbidities. Methods: Comprehensive review based on PubMed search (January 2020–January 2025). Results: The studies (n = 14) included 2623 patients (N = 1158 underwent unilateral adrenalectomy), aged 18–93 (mean = 57.49 years), with a female-to-male ratio = 1.54. Post-adrenalectomy (n = 9, N = 753) analysis: the PSAI risk correlated with the severity of baseline hypercortisolism. PSAI incidence: 50% of MAC. The rate after 4–6 weeks follow-up was 71.9% (adrenal Cushing’s syndrome) vs. 50% (MACS) vs. 14.4% (NFA). PSAI duration was up to 35 months. Early PSAI diagnosis was reflected by post-operative cortisol assay on day 1 (cut-off ≤ 5 µg/dL) and an ACTH (Cosyntropin) stimulation test (CST) (cortisol cut-off ≤ 14 µg/dL). Pre-operatory PSAI predictors: higher serum cortisol-DST (1 mg dexamethasone testing) and lower baseline plasma ACTH (not all studies agreed). Conclusions: A stratified strategy is encouraged following a unilateral adrenalectomy in MACS; PSAI is expected in almost half of patients, with a potential improvement of hypertension. Serum cortisol assays serve as most useful biomarker as pre-operatory PSAI predictor (after DST) and, potentially, in addition with baseline ACTH. Post-surgery basal cortisol measurement (± CST) helps the decision of glucocorticoids replacement since first post-operative day and during follow-up, serial testing at 3 months is a useful tool. Full article

Background: Paediatric hepatocellular carcinoma (HCC), including its fibrolamellar variant (FLC), is a rare malignancy with distinct biological behaviour and limited therapeutic options. While complete surgical resection is a key determinant of survival, many patients present with unresectable tumours at diagnosis. The role of neoadjuvant chemotherapy in improving resectability, particularly in histologically distinct subtypes, remains inconclusive. Methods: We retrospectively analysed 43 patients (<18 years) with histologically confirmed conventional HCC (cHCC, n = 27) or FLC (n = 16) enrolled in the German Pediatric Liver Tumour Registry. We assessed clinical characteristics, treatment response, surgical outcomes, and survival. Special focus was placed on the impact of neoadjuvant chemotherapy in initially unresectable tumours. Results: FLC and cHCC exhibited significant differences in clinical presentation, such as age of presentation, AFP elevation, or presence of underlying liver disease. Although overall survival did not significantly differ between groups, cHCC tumours showed a markedly higher response to chemotherapy (62.5% partial remission vs. 0% in FLC). Complete resection (R0) was achieved in 77% of all patients and was the strongest predictor of survival. Importantly, a subset of cHCC patients who initially had unresectable tumours became eligible for curative surgery following neoadjuvant chemotherapy. Notably, delayed resection after chemotherapy led to outcomes comparable to those with upfront surgery, whereas progression during chemotherapy was associated with a universally poor prognosis. Conclusions: This study supports upfront resection as the preferred strategy in paediatric HCC and FLC whenever feasible. In cHCC, neoadjuvant chemotherapy demonstrated a favourable response profile and contributed to secondary resectability in a subset of initially unresectable cases, supporting a potential role within a multimodal treatment approach. In contrast, FLC showed limited responsiveness to current systemic therapies. These findings emphasise the importance of histology-specific strategies and highlight the ongoing need for more effective systemic options, particularly for unresectable FLC. Full article

Glioblastoma is the most common and aggressive malignant primary brain tumour. Patients with glioblastoma have a median survival of only around 14.6 months after diagnosis, despite the availability of various conventional multimodal treatments including chemotherapy, radiation therapy, and surgery. Therefore, photodynamic therapy (PDT) has emerged as an advanced, selective and more controlled therapeutic approach, which has minimal systemic toxicity and fewer side effects. PDT is a less invasive therapy that targets all cells or tissues that possess the photosensitizer (PS) itself, without affecting the surrounding healthy tissues. Polymeric NPs (PNPs) as carriers can improve the targeting ability and stability of PSs and co-deliver various anticancer agents to achieve combined cancer therapy. Because of their versatile tuneable features, these PNPs have the capacity to open tight junctions of the blood–brain barrier (BBB), easily transport drugs across the BBB, protect against enzymatic degradation, prolong the systemic circulation, and sustainably release the drug. Conjugated polymer NPs, poly(lactic-co-glycolic acid)-based NPs, lipid–polymer hybrid NPs, and polyethylene-glycolated PNPs have demonstrated great potential in PDT owing to their unique biocompatibility and optical properties. Although the combination of PDT and PNPs has great potential and can provide several benefits over conventional cancer therapies, there are several limitations that are hindering its translation into clinical use. This review aims to summarize the recent advances in the combined use of PNPs and PDT in the case of glioblastoma treatment. By evaluating various types of PDT and PNPs, this review emphasizes how these innovative approaches can play an important role in overcoming glioblastoma-associated critical challenges, including BBB and tumour heterogeneity. Furthermore, this review also discusses the challenges and future directions for PNPs and PDT, which provides insight into the potential solutions to various problems that are hindering their clinical translation in glioblastoma treatment. Full article

Artificial Intelligence (AI) and computer-aided diagnosis (CAD) have revolutionised various aspects of modern life, particularly in the medical domain. These technologies enable efficient solutions for complex challenges, such as accurately segmenting brain tumour regions, which significantly aid medical professionals in monitoring and treating patients. This research focuses on segmenting glioma brain tumour lesions in MRI images by analysing them at the pixel level. The aim is to develop a deep learning-based approach that enables ensemble learning to achieve precise and consistent segmentation of brain tumours. While many studies have explored ensemble learning techniques in this area, most rely on aggregation functions like the Weighted Arithmetic Mean (WAM) without accounting for the interdependencies between classifier subsets. To address this limitation, the Choquet integral is employed for ensemble learning, along with a novel evaluation framework for fuzzy measures. This framework integrates coalition game theory, information theory, and Lambda fuzzy approximation. Three distinct fuzzy measure sets are computed using different weighting strategies informed by these theories. Based on these measures, three Choquet integrals are calculated for segmenting different components of brain lesions, and their outputs are subsequently combined. The BraTS-2020 online validation dataset is used to validate the proposed approach. Results demonstrate superior performance compared with several recent methods, achieving Dice Similarity Coefficients of 0.896, 0.851, and 0.792 and 95% Hausdorff distances of 5.96 mm, 6.65 mm, and 20.74 mm for the whole tumour, tumour core, and enhancing tumour core, respectively. Full article

Background: Around one-quarter of all people in the developed world die of cancer, with primary care being the main setting in which the disease is first suspected because the majority of patients consult a general practitioner (GP) when they present with symptoms. Diagnostic delay may thus be attributable to the patient, the GP, or the healthcare system. While some findings suggest that as much as half of the total delay consists of patient delay, more research is nonetheless needed into how GPs can facilitate access to diagnostic evaluation when patients experience symptoms. Methods: A retrospective observational study will be conducted to evaluate a cohort of patients diagnosed with cancer, with data being obtained from both primary and specialised care settings. Different time intervals will be analysed, dating from onset of first symptoms to diagnosis or initiation of treatment, and will be classified as: patient interval; primary-care interval; healthcare-system interval; diagnostic interval; treatment interval; and total interval. Study variables will include patient characteristics (socio-demographic, risk factors, morbidity, etc.), tumour characteristics (tumour stage, symptom onset, alarm symptoms, etc.), and healthcare characteristics (place of initial consultation, referral to specialised care, etc.). Discussion: The study will describe diagnostic delays in patients with cancer in primary care, considering the time elapsed between symptom onset and initial consultation, request for tests and/or patient referral, first evaluation in the hospital setting, and date of diagnostic confirmation and treatment initiation. Additionally, the study will make it possible to identify the patient-, healthcare-, and disease-related variables that intervene in the duration of such delays. Full article

Background: Pancreatic cancer is frequently identified as the cancer type with the shortest probable survival time after diagnosis, and efforts to develop successful treatments have had a very limited impact in the clinic. One reason for the limited therapeutic options is the lack of appealing drug targets. The great majority of pancreatic cancers are classified as Pancreatic Ductal Adenocarcinoma (PDAC), in which the genetic landscape is dominated by four genes: KRAS, TP53, CDKN2A, and SMAD4. However, despite extensive knowledge of these genetic drivers, the development of effective therapies has seen only very limited success. Methods: Existing evidence indicates that mutations in the tumour suppressor gene PTEN are uncommon in PDAC (<10% cases). However, the loss of PTEN function through non-genetic mechanisms may be much more common and have a strong impact. We therefore summarise and review a large body of immunohistochemical studies that address the loss of PTEN in PDAC as well as a smaller number of studies addressing other implicated proteins, including KDM6A and ARID1A. Results: These studies show some loss of PTEN protein in more than half of PDAC cases. Furthermore, although genetic changes in genes including KDM6A/UTX and ARID1A are also uncommon, reduced expression of their encoded proteins is observed in many, perhaps most, cases of PDAC. Conclusions: These analyses, which go beyond genetics, highlight the broader set of cellular functions that are dysregulated in many pancreatic cancers and provide broader opportunities for treatment strategies. This review highlights the emerging importance of other drivers in PDAC, which are less well-studied in this context. Full article

Angioimmunoblastic T-cell lymphoma (AITL) is a rare and aggressive subtype of non-Hodgkin lymphoma, the monitoring of which is largely restricted to radiological methods. Diagnosis relies on identifying characteristic clinicopathological features, supported by the detection of recurrent somatic mutations in RHOA, TET2, IDH2 and DNMT3A. The characteristic molecular profile of AITL and the high levels of circulating tumour DNA (ctDNA) measurable in AITL before treatment makes this an attractive lymphoma subtype in which to further investigate the role of ctDNA monitoring. The detection of somatic mutations in pre-treatment AITL-containing tissue samples was compared to those detected in pre-treatment ctDNA samples in a cohort of 12 patients. Changes in ctDNA somatic mutation burden over time were then correlated with radiological response. All six paired pre-treatment ctDNA and tissue samples had variants in common. All (8/8) previously ctDNA-detectable IDH2 and RHOA variants were undetectable in ctDNA samples at the time of end-of-treatment complete metabolic response (CMR). In comparison, the majority of both previously ctDNA-detectable DNMT3A variants (3/4) and TET2 variants (6/11) were detectable in ctDNA samples at the time of end-of-treatment CMR. These observations suggest that IDH2/RHOA variants may be more reliable markers of measurable residual disease in AITL than DNMT3A/TET2 variants. Full article

Breast cancer is one of the most commonly diagnosed malignant tumours in women worldwide. Although modern medicine has led to advanced diagnostic methods and therapies that allow for increasingly effective treatment, the mechanisms underlying breast cancer development and progression remain the subject of intensive research. In the pathogenesis of this cancer, significant importance is attributed to interactions between tumour cells and the tumour microenvironment, in which soluble immune system mediators—cytokines—play a key role, including IL-21 and IL-22. These interleukins, by modulating the immune response, can both promote and inhibit tumour progression, and analysing their concentrations may prove helpful in diagnosis, disease progression prognosis, and the development of new therapies, including immunotherapy. The aim of this study was to determine the concentrations of IL-21 and IL-22 in a group of patients with invasive cancer, depending on the biological type of the tumour and its malignancy grade. The study involved 60 women with breast cancer and 20 women with benign breast lesions, and the analysis of IL-21 and IL-22 protein concentrations was performed using the enzyme-linked immunosorbent assay (ELISA) method. The analysis shows that the concentrations of IL-21 and IL-22 do not differ significantly depending on the malignancy grade of the tumour. However, a statistically significant negative correlation between the concentrations of IL-21 and IL-22 was observed exclusively in the group of patients with benign breast lesions. Due to the high heterogeneity of breast cancers, further research with a larger study group is necessary to better understand these parameters and possibly apply them clinically in patients with breast cancer. Full article

In the management of cholangiocarcinoma, effective biliary drainage and accurate diagnosis are vital to allow further treatment. Confirmation of tissue diagnosis and molecular characterization is also required to guide future treatment options including surgery and chemotherapy as well as the possible use of personalized treatments that target specific mutations present within individual tumours. Initial CT or MRI scans may be followed by endoscopic ultrasound (EUS) or endoscopic retrograde cholangiopancreatography (ERCP) to obtain tissue samples. However, these methods often fall short due to difficulty in accessing entire bile duct strictures. SpyGlass cholangioscopy can improve diagnosis, yet may fail to provide sufficient tissue for molecular characterization. Here we present a perspective on the development of snake-like agile robots with integrated optical imaging and Raman spectroscopy. These robots could improve the mapping of the biliary tree and the precision of biopsy collection and allow tissue analysis in situ, as well as facilitating stenting to restore the flow of bile. A multidisciplinary approach that brings together clinicians, pathologists, and engineers is required to develop these new robotic technologies and improve patient outcomes. Full article

In November 2024, the fourth annual Symposium focusing on early-age onset cancer (EAOC) was hosted by the Colorectal Cancer Resource & Action Network (CCRAN), assembling clinicians, researchers, and patients virtually to discuss challenges in early detection and diagnosis of individuals afflicted with EAOC across tumour types. The meeting addressed the rising rates of EAOC and identified strategies to overcome barriers to timely detection and diagnosis by closing gaps in public and healthcare provider knowledge on symptoms of cancer in younger adults and reducing inequities in standard screening for younger age groups. Discussions also encompassed the various factors that serve as impediments to accessing diagnostic testing and obtaining results, as well as the critical need for access to diagnostics such as comprehensive genomic profiling (CGP), the results of which could be imperative in helping to guide clinical decisions regarding effective and well-tolerated targeted therapies. The Symposium generated key calls to action regarding increasing EAOC education and awareness among primary care providers and the public, re-evaluation of cancer screening programs’ eligibility criteria to include younger populations, and mechanisms to reduce waiting times for diagnostic testing by addressing technologist shortages and improving access to CGP through national collaborative strategies and increased funding. Full article

Background: We present an interesting case involving a tumour comprising both basal cell tumour cells and sarcomatoid tumour cells. An 86-year-old woman presented with an erythematous lesion on her left cheek. Clinical and dermoscopic findings suggested BCC. Complete excision and histopathological examination revealed a BCC with a separate proliferation of atypical spindle and epithelioid cells. Immunohistochemical staining supported the diagnosis, with basaloid cells positive for CK5/6 and Ber-EP4 and sarcomatoid cells positive for CD10 and vimentin. Results: Histology and immunohistochemistry confirmed a basal cell carcinoma with sarcomatoid differentiation. The close proximity of sarcomatoid cells to the BCC component suggests a potential role of epithelial–mesenchymal interactions in tumour development. Further investigations into the exact origin of this tumour are required. Conclusion: Basal cell carcinoma with sarcomatoid differentiation is rare. This case highlights the importance of thorough histological and immunohistochemical evaluation. Further studies are necessary to better understand the pathogenesis of such collision tumours. Full article

Primary hepatic gastrointestinal stromal tumours (PHGISTs) are rare and frequently misdiagnosed due to their atypical presentation and uncertain origin. The purpose of this article is to present the case of a 79-year-old female patient with a gigantic PHGIST characterized by a predominantly cystic nature—an extremely rare presentation, as most cases of PHGIST are solid. Despite extensive imaging and exploratory laparotomy, the primary origin remained uncertain, leading to questioning about whether it was a true primary hepatic GIST or an atypical metastatic lesion. The initial therapeutic approach involved a surgical procedure aimed to confirm the diagnosis and achieve reductive tumourectomy. Following the surgery, the patient was administered imatinib with a favourable clinical response for four and a half years—an atypical pattern of resistance, as most patients typically develop therapeutic resistance within two to three years. A second surgical intervention was performed to address a cystic lesion localized in the left hepatic lobe, followed by an atypical segment III hepatectomy to achieve macroscopic resection. Subsequently, the patient received sunitinib for two and a half years, which resulted in temporary disease stabilization. However, the sunitinib treatment was associated with hypertension and leukopenia. The patient’s overall survival was 8 years, suggesting that individualized therapeutic strategies and close monitoring might be the key in such cases. Furthermore, this case confirms the role of surgical intervention even in advanced disease stages, with multiple major resections contributing significantly to prolonged survival. The interplay between surgical and oncologic therapies remains essential to guiding clinical decisions. Given the unusual cystic presentation, this case highlights the necessity to expand the pathological and molecular profiling of PHGISTs. Furthermore, the atypical timeline of resistance development and treatment-related toxicity emphasizes the importance of further research into the genetic and pharmacological determinants of PHGISTs. These findings advocate for the refinement of diagnostic, therapeutic, and surveillance protocols tailored to rare GIST subtypes. Full article

Background: Interdigitating dendritic cell sarcoma (IDCS) is a very rare haematologic malignant tumour that arises from antigen-presenting cells. While it primarily affects the lymph nodes, extranodal manifestations have been observed, and there is a slight male predominance. Due to its rarity, diagnosing IDCS can be challenging, as illustrated in our case report of a 61-year-old woman. Methods: In this case presentation, the oncological management of a patient suspected of having malignant melanoma metastasis in the neck lymph nodes is discussed. This includes otorhinolaryngological examinations, fine needle aspiration biopsy, PET CT imaging, and histological analysis with immunohistochemistry. Results: The patient’s medical history included the excision of a pigmented lesion from the left ala of her nose, which was diagnosed as malignant melanoma. After surgical treatment, she experienced a tumour-free period of one year; however, during a follow-up ultrasonography three pathological lymph nodes were detected on the left side of her neck. Initially, a nodal metastasis of melanoma was suspected. Yet, fine needle aspiration cytology revealed myofibroblastic tumour invasion, and a re-biopsy showed no signs of malignancy. To further investigate, PET-CT scans were conducted, and a modified radical neck dissection was performed based on the findings. The histological analysis of the lymph nodes revealed an IDCS, a second independent tumour distinct from the initially diagnosed malignant melanoma, originating from the submandibular, upper jugular, and mid-jugular lymph nodes. Conclusions: This case highlights the diagnostic difficulties associated with IDCS. Initially, the clinical suspicion of malignant melanoma was considered, necessitating further examinations and a multidisciplinary approach to reach a final diagnosis and provide the patient with appropriate treatment. Full article