Search Results (1,239)

Background: Borderline ovarian tumors (BOTs) represent a distinct group of rare epithelial ovarian neoplasms with excellent prognosis, but persistent uncertainty in patient understanding and clinical management. This study evaluated disease awareness, perceptions, and treatment patterns among affected women in Germany. Methods: The national multicenter Expression VIII survey was conducted across 34 centers by the North-Eastern German Society of Gynecologic Oncology (NOGGO). Using a standardized 46-item questionnaire, 286 patients with BOTs provided data on symptoms, treatment, fertility, follow-up, and illness perception. Descriptive analyses were performed. Results: Most participants (mean age 51 years) underwent surgery (94%), while systemic therapy was infrequent (chemotherapy 9%, bevacizumab 4%). Fertility-sparing surgery was performed in 14% overall, corresponding to 71% of those desiring future childbearing. Although 81% identified their physician as their main information source and rated information quality highly (mean 8.6/10), 29% believed they had ovarian cancer and 64% were unaware of their tumor stage. Nearly all patients (97%) received regular follow-up, though 18% were uncertain about the procedures performed. Disease severity was rated moderately high (mean 5.4/10), and recurrence risk and mortality were often overestimated. Conclusions: Despite good overall physician communication, substantial misconceptions persist among patients with BOTs, including the mistaken belief that they have been diagnosed with cancer, suggesting a need for clearer, structured education about its favorable prognosis and management of the disease. Improved guideline adherence and treatment centralization in specialized centers may reduce overtreatment and optimize fertility-preserving approaches. Full article

Background/Objectives: Myelofibrosis (MF) is a clonal myeloproliferative neoplasm driven by dysregulated JAK-STAT signaling, characterized by progressive marrow fibrosis, splenomegaly, constitutional symptoms, and increased risk of leukemic transformation. Allogeneic hematopoietic stem cell transplantation (allo-HCT) remains the only potentially curative intervention. In Italy, allo-HCTs for myeloproliferative neoplasms (MPN, i.e., myelofibrosis, polycythaemia vera, and essential thrombocythaemia combined) increased by 163% from 2015 to 2025; MF-specific procedure counts were not separately available in this registry export, so this figure should not be read as MF-specific, with MPN accounting for 8% of all allogeneic procedures (n = 171) in 2025, showing a 29.5% year-on-year increase from 2024. Concurrently, the demographic profile shifted, with individuals aged 60 and over representing 38% of all recipients, surpassing other age groups for the first time in 2025. Results: This review synthesizes current evidence on transplant indications and timing, pre-transplant management, donor selection, and conditioning regimen optimization, emphasizing the emerging role of treosulfan-based and dual-alkylator platforms, including the thiotepa–treosulfan–fludarabine (TTF) regimen. Post-transplant molecular MRD monitoring and relapse management are also discussed. Three-year overall survival in myelofibrosis ranges from about 59% to 67%, depending on donor type, with outcomes improving due to better patient selection, optimized conditioning, and supportive care. Conclusions: Prospective randomized trials are urgently needed to validate optimal conditioning intensity, the role of novel JAK inhibitors in the peri-transplant period, and MRD-guided pre-emptive strategies. Full article

Pulmonary hypertension (PH) is an increasingly recognized complication of Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs). Recent data suggest prognostic implications of both cardiovascular morbidity and mortality and hematologic progression. Additionally, PH and MPNs share common pathophysiologic mechanisms that bridge these two seemingly different disorders. The landscape of PH in MPNs is evolving in the face of improved survivorship and reduced disease progression, leading to increased incidence and prevalence of concurrent and/or consequent cardiovascular disease. Prospective studies are necessary to refine screening protocols, risk stratification, and prognostic and therapeutic implications of PH in this population. Full article

Background/Objectives: Borderline ovarian tumours (BOTs) are distinct epithelial neoplasms with excellent survival but variable recurrence, including late relapse and occasional malignant transformation. Follow-up strategies remain inconsistent internationally, with no standardised, risk-adapted framework. We aimed to synthesise the evidence on BOT recurrence patterns, risk factors and surveillance strategies, and to propose a structured, risk-adapted surveillance framework. Methods: This is a narrative expert synthesis rather than a systematic review. Three evidence sources were combined: our previously published comprehensive review of BOTs, our recent meta-analysis of recurrence and malignant transformation, and an appraisal of contemporary international guidelines. Clinicopathological and surgical determinants of recurrence were then mapped onto the available follow-up tools through a three-step approach, and the resulting risk strata, surveillance intervals and total follow-up duration were agreed on by consensus within a single tertiary gynaecological oncology centre (the “Barts Framework”). Results: Recurrence occurs in 3–10% of patients, with up to one-third arising beyond five years. Key predictors include fertility-sparing surgery (particularly cystectomy), incomplete staging, advanced stage, residual disease, and adverse histological features such as micropapillary/cribriform architecture and invasive implants. Three targets for surveillance were identified: early detection of recurrence, detection of malignant transformation, and optimisation of fertility. Transvaginal ultrasound emerged as the cornerstone modality, with cross-sectional imaging and tumour markers applied selectively. Four risk strata were derived, each specifying follow-up intensity, modality, total duration and care setting. Low-risk patients can be managed in decentralised settings (gynaecological units), whereas high-risk groups warrant specialist oversight (gynaecological oncology centres). Patient-initiated follow-up is incorporated to minimise unnecessary interventions. Conclusions: This risk-adapted approach provides a scalable framework to standardise BOT surveillance whilst reducing overuse and maintaining oncological safety. The framework is consensus-based and single-institution in origin, and prospective external validation with long-term outcome data is required before wider adoption. Integration of molecular stratification and artificial-intelligence-assisted imaging represents a key future direction. Full article

Background/Objectives: The COVID-19 pandemic disrupted gynecologic care pathways and required stricter prioritization of surgical treatment. We evaluated whether the pandemic restriction period was associated with changes in the characteristics of women with adnexal masses reaching surgery and explored ADNEX discrimination within the histologically verified surgical cohort. Methods: This retrospective single-center study included all consecutive women evaluated for an adnexal mass in a dedicated gynecologic ultrasound clinic during a pre-pandemic baseline period and a COVID-19 restriction period. Ultrasound examinations were performed by the same expert using International Ovarian Tumor Analysis (IOTA) terminology and the IOTA Assessment of Different NEoplasias in the adneXa (ADNEX) score was calculated prospectively at the time of examination. Histological analyses were restricted to surgically managed patients. Results: Overall, 340 women were evaluated in the non-COVID period and 211 during the COVID period; 149 (43.8%) and 40 (19.0%), respectively, underwent surgery. After exclusion of five adolescents from the pre-pandemic group, 144 and 40 operated patients were analyzed. The COVID-era surgical cohort was older (median 52.0 vs. 39.0 years, p = 0.0053), had higher ADNEX scores (median 13.7% vs. 4.4%, p = 0.0010), and had a higher proportion of borderline or malignant histology (32.5% vs. 13.2%, p = 0.0083). In an exploratory pooled logistic model, ADNEX score and COVID-period status were associated with non-benign histology. The AUCs were 0.789 and 0.905 in the COVID and non-COVID surgical cohorts, respectively, without a statistically significant between-cohort difference (p = 0.169). Conclusions: The COVID-19 restriction period was associated with a lower proportion of evaluated women proceeding to surgery and with enrichment of the operated cohort for older patients and lesions with higher sonographic risk and non-benign histology. Because surgical selection itself depended partly on ultrasound findings and outcomes were unavailable for non-operated women, these data should not be interpreted as independent validation of ADNEX or proof that deferred management was safe. Full article

While pathogenic germline CHEK2 variants are known to increase cancer risk, there is currently insufficient evidence regarding the precise risk of developing malignant neoplasms associated with specific missense variants or variants of uncertain significance. As a result, no clear clinical guidelines exist regarding consultation, monitoring and specific treatment options for those patients. For the first time in Russia, clinical data and whole-genome sequencing (WGS) results were analyzed for 3150 patients with cancer and suspected hereditary cancer syndromes (HCS) and 5163 healthy individuals. This dataset formed the basis for assessing the role of germline CHEK2 variants in the development of different cancer types. The chromosomal coordinates and coding sequence coordinates are given in accordance with the GRCh38 (hg38) genome assembly and the NM_007194.4 transcript. Pathogenic (P) and likely pathogenic (LP) variants of CHEK2 significantly increased the risk of breast cancer (OR = 2.015 [95% CI: 1.27–3.21]; p = 0.0031), but the association with colorectal cancer was not statistically significant (OR = 1.354 [95% CI: 0.42–4.42]; p = 0.616). A moderate increase in cancer risk was identified for the c.1100del variant (OR = 2.263 [95% CI: 1.19–4.32]; p = 0.0132) and for the common P/LP variants c.1100del, c.444+1G>A and c.433C>T (OR = 2.219 [95% CI: 1.40–3.51]; p = 0.0007). Notably, our study confirmed that CHEK2 c.470T>C (p.Ile157Thr) is the most common variant in the patient group, identified in 3.8% of cases (120/3150), compared with 3.0% in the control group (155/5163). Although the association between the most common CHEK2 variant c.470T>C and cancer risk reached nominal statistical significance (OR = 1.279 [95% CI: 1.00–1.63]; p = 0.0463), the effect size was minimal, suggesting that the contribution of this variant to hereditary cancer risk in the Russian population is modest. Additional studies are required before this variant can be definitively excluded from clinical interpretation. Full article

Objectives: A percutaneous native kidney biopsy remains the gold standard for diagnosing glomerular, tubulointerstitial and vascular kidney diseases. Although generally safe, it may cause major haemorrhagic complications. Using the French national registry, Kaczmarek et al. developed a simplified bleeding risk score (anaemia, female sex, heart failure, acute kidney injury; range: 0–5), achieving an AUC of 0.755 in native biopsies. We aimed to externally validate this score in a Romanian cohort and to assess whether additional clinically relevant predictors could improve discrimination for major bleeding. Methods: We conducted a retrospective cohort study of all consecutive adults undergoing an ultrasound-guided percutaneous native kidney biopsy at a tertiary nephrology centre in Romania between January 2008 and December 2024. The primary outcome was a composite major bleeding event: clinically significant haematoma or haemorrhage, blood transfusion, angiographic intervention or nephrectomy. The Kaczmarek score was validated using a receiver operating characteristic (ROC) analysis. Candidate predictors were assessed by multivariable logistic regression, and a simplified score was derived from the regression coefficients. Results: Among 3081 patients, 162 (5.3%) experienced major bleeding. The Kaczmarek score showed modest discrimination (AUC: 0.624, 95% CI: 0.585–0.663). In the multivariable analysis (n = 2506 complete cases), anaemia, heart failure, solid neoplasm and fibrinogen were independently associated with major bleeding. An eight-component score (anaemia, heart failure, solid neoplasm, and fibrinogen < 511 mg/dL; female sex, hypertension, liver disease, and eGFR < 30 mL/min/1.73 m²) achieved an AUC of 0.676 (95% CI: 0.631–0.717), outperforming the Kaczmarek score. Conclusions: The French score performed only modestly in our cohort. Adding comorbidities, kidney function and haemostatic parameters, particularly fibrinogen, improved the risk discrimination. Full article

Radiation-induced liver disease (RILD) remains a clinically significant complication of radiotherapy for malignant neoplasms of the liver and upper abdomen, restricting achievable therapeutic doses and adversely affecting patient outcomes. Conventional photon-based radiotherapy (X-rays/γ-rays) exposes substantial volumes of healthy liver parenchyma and adjacent organs to ionizing radiation, increasing the risk of hepatocellular damage, inflammation, and progressive fibrosis. Electron irradiation (β-particles) represents a promising alternative owing to its limited tissue penetration (~2–3 cm) and steep dose fall-off, which significantly reduces exit dose and may reduce exit dose and limit exposure of paratumoral healthy tissues compared with photon therapy. However, the molecular mechanisms underlying electron-induced hepatic damage and strategies for its prevention remain insufficiently characterized. This review systematically analyzes the pathogenesis of radiation-induced liver damage, encompassing direct DNA damage, oxidative stress, mitochondrial dysfunction, NF-κB-mediated inflammation, cellular senescence, and TGF-β/Smad-driven fibrosis. The comparative dosimetric and radiobiological advantages of electron irradiation over photon therapy are discussed, with particular attention to intraoperative radiotherapy, FLASH, and very high-energy electron techniques. Current radioprotective strategies are critically evaluated, with emphasis on the limitations of amifostine and the multifunctional radioprotective potential of ascorbic acid, including free radical scavenging, attenuation of lipid peroxidation, stimulation of endogenous antioxidant defense, and direct inhibition of radiation-induced DNA strand breaks. Existing gaps in the evidence base are identified, and recommendations for future experimental and clinical research are proposed. Full article

Epithelioid sarcoma (EPS) is an ultra-rare malignant mesenchymal neoplasm of uncertain differentiation that comprises two distinct clinicopathological subtypes: classic and proximal. Classic EPS most commonly occurs in the distal upper extremity of adolescents and young adults, whereas proximal-type EPS most often affects the truncal regions of young to middle-aged adults. Both classic and proximal-type EPSs exhibit aggressive clinical behavior, including a higher risk of local recurrence and regional lymph node or distant metastasis. Histologically, classic EPS is characterized by irregular nodules composed of epithelioid and spindled cells, while proximal-type EPS consists of multinodular distributions and sheets of large polygonal cells. EPS has a distinctive immunoprofile with characteristic expression of cytokeratins and epithelial membrane antigen. Loss of nuclear expression of SMARCB1 protein occurs in the vast majority of cases. Moreover, SMARCB1 homozygous deletions have also been observed in both subtypes. Surgery is the mainstay treatment approach for localized EPS. Systemic treatment options for metastatic or unresectable locally advanced disease are very limited. The withdrawal of tazemetostat has created a significant gap in available treatment options. In this review, we provide an overview of the current knowledge on the clinical and radiological features, histopathology, immunohistochemistry, pathogenesis, and management of EPS. Full article

Background and objectives: Melanoma survivors may develop additional primary malignancies, but data from Eastern European hospital cohorts are scarce. We aimed to estimate the observed incidence of second primary cancers (SPCs) within a Romanian referral-centre cohort, identify associated factors, and explore the association of SPC occurrence with overall survival. Methods: We conducted a retrospective, hospital-based cohort study of 394 patients with histopathologically confirmed cutaneous melanoma followed at two referral centres in Cluj-Napoca. Additional malignancies were counted as new primaries only when clinical and/or histopathological documentation distinguished them from recurrence or metastasis. Incidence density was expressed per 1000 person-years. Multivariable logistic regression assessed age, sex, residence, and Breslow thickness. Fixed-covariate Cox and Kaplan–Meier analyses were considered exploratory because of immortal-time and competing-risk limitations. Results: Over 1848 person-years, 79 patients (20.1%) developed at least one SPC (131 events; observed incidence 70.9/1000 person-years), most frequently cutaneous (53.6/1000 person-years). SPC occurrence increased with age (Cochran–Armitage Z = 5.63, p < 0.001); the Kaplan–Meier complement estimate reached 20.7% at five years. Age independently predicted SPC (OR 1.86 per decade, p < 0.001), whereas greater Breslow thickness was inversely associated (OR 0.86, p = 0.008). Actinic keratosis showed a strong unadjusted association (OR 6.64, p < 0.001) but was not included in the adjusted model. The fixed-status Cox model showed lower mortality among patients with an SPC (HR 0.36, p < 0.001), a finding vulnerable to detection and immortal-time bias. Conclusions: SPCs were frequent in this hospital cohort and predominantly cutaneous. Older age was an independent predictor, while actinic keratosis was a strong unadjusted marker. Prospective, population-based validation is needed before surveillance intensity is individualised. Full article

Background/Objectives: Bevacizumab is widely used at recurrence in glioblastoma, but comparisons are complicated by multimodal treatment selection and progression assessment. We examined outcomes associated with a bevacizumab-containing first-recurrence strategy and explored the components of post-recurrence progression-free survival (prPFS). Methods: This retrospective single-center cohort included 166 patients at first recurrence: 114 received a bevacizumab-containing strategy and 52 a non-bevacizumab strategy. Of these, 163 had evaluable outcomes. Local therapy at first recurrence was recorded in 19.3% and 90.4% of the groups, respectively. Treatment strategy was fixed at first recurrence to reduce immortal-time bias. Analyses used pretreatment covariates, multiple imputation, propensity-score overlap weighting, robust variance estimation, and competing-risk methods. Complete-case adjusted models included 117 patients. Recurrence-specific performance status, corticosteroid exposure, and MGMT status were unavailable. Results: Among 163 patients, 136 deaths and 145 prPFS events occurred. In the overlap-weighted analysis after multiple imputation, a bevacizumab-containing strategy was not associated with improved post-recurrence overall survival (OS; HR 1.40, 95% CI 0.93 to 2.10) or prPFS (HR 0.81, 95% CI 0.55 to 1.18). Competing-risk analysis showed a lower cause-specific hazard of documented second progression (HR 0.29, 95% CI 0.16 to 0.53) and a higher cause-specific hazard of death before documented progression, although its CI included the null (HR 1.65, 95% CI 0.93 to 2.93). Higher baseline neutrophil-to-lymphocyte ratio was associated with poorer OS (HR per doubling 1.49, 95% CI 1.20 to 1.85), but treatment interactions were inconsistent across parameterizations. Conclusions: A bevacizumab-containing first-recurrence strategy was not associated with improved post-recurrence OS or prPFS. Divergent progression and death patterns caution against interpreting progression-based endpoints as direct evidence of disease control in this observational setting. Full article

Background/Objectives: Outcomes after perioperative FLOT for gastric and gastroesophageal junction adenocarcinoma remain variable, even among patients treated with curative intent. Although postoperative pathological findings are central to risk assessment, they do not fully capture patient-related factors that may influence recovery, treatment completion, and survival. This multicenter study evaluated routinely available clinical, laboratory, and pathological variables and assessed whether integrating these variables could improve postoperative prognostic stratification. Methods: We retrospectively analyzed 173 patients with locally advanced gastric or gastroesophageal junction adenocarcinoma treated with perioperative FLOT across seven oncology centers in Türkiye. Overall survival (OS) was the primary endpoint. Baseline inflammatory/nutritional status, pretreatment carcinoembryonic antigen (CEA), postoperative nodal status, and comorbidity burden were assessed. An exploratory modified FLOT Prognostic Score (mFPS) was constructed by assigning one point each for high inflammatory/nutritional risk, elevated CEA, ypN-positive disease, and age-adjusted Charlson Comorbidity Index ≥ 5. Results: At a median follow-up of 39.7 months, median OS was 41.4 months, with estimated 2-year and 5-year OS rates of 69% and 44%, respectively. Surgery was performed in 164 patients, and 83 patients completed planned adjuvant chemotherapy. In multivariable analysis, ypN-positive disease, higher comorbidity burden, and high inflammatory/nutritional risk were independently associated with shorter OS. Among the 126 patients with complete data available for all score components, the mFPS stratified patients into groups with significantly different outcomes: median overall survival was not reached in the low-risk group, compared with 56.1 months in the intermediate-risk group and 18.7 months in the high-risk group. Conclusions: Survival after perioperative FLOT was not determined by residual disease burden alone. Integrating postoperative nodal status with baseline host-related factors may help identify patients at increased risk of adverse outcomes following curative-intent treatment. The proposed score should be considered exploratory and requires external validation before clinical application. Full article

Clonal hematopoiesis of indeterminate potential (CHIP) is an age-associated premalignant state defined by somatic mutations in hematopoietic cells at a variant allele frequency (VAF) ≥2% in the absence of overt hematologic malignancy. Among CHIP-associated mutations, JAK2 V617F is of particular interest because it occupies a dual biological and clinical role: it is both the principal driver of BCR::ABL1-negative myeloproliferative neoplasms (MPNs) and a clonal hematopoiesis variant conferring approximately 12-fold cardiovascular risk in selected cohorts, exceeding that reported for common DTA CHIP variants. Quantitative assessment of JAK2 V617F allele burden is therefore clinically relevant across the full disease continuum—from subclinical clonal expansion to MPN diagnosis, prognostic stratification, and therapeutic monitoring—as VAF thresholds correlate with disease phenotype, thrombotic risk, molecular response, and fibrotic progression. Digital PCR platforms, including droplet digital PCR (ddPCR) and chip-based digital PCR, have emerged as highly sensitive and reproducible methods for absolute JAK2 V617F quantification without the need for standard curves, with reported limits of detection as low as 0.01%. In this review, we synthesize current evidence on the molecular biology of JAK2-driven clonal hematopoiesis, the clinical significance of allele burden quantification, and the analytical performance of digital PCR compared with quantitative PCR and next-generation sequencing. We interpret these findings through a systems biology lens that draws together JAK-STAT signaling networks and thrombo-inflammatory pathways including inflammasome-dependent IL-1 signaling, clonal architecture, and bone marrow microenvironmental remodeling. We also discuss published quantitative models in which JAK2 V617F allele burden is treated as a dynamic state variable, while emphasizing that the present review offers a conceptual synthesis rather than a new computational model. We provide a structured comparative synthesis of published digital PCR analytical performance data, a stage-adapted proposal for clinical monitoring, and schematic models to guide future implementation. Overall, the evidence supports digital PCR as a precision tool for monitoring JAK2 V617F clonal dynamics across the CHIP–MPN spectrum, and points to several priorities: assay standardization, harmonized reporting, external quality assessment, and prospective clinical validation. Full article

Introduction. Mortality rates from malignant neoplasms can be considered a key marker of adverse environmental impacts. The aim of this study was to assess the association between exposure to ionizing radiation and the risk of mortality from malignant neoplasms among the population of Kazakhstan living in areas adjacent to the Semipalatinsk Nuclear Test Site (SNTS). Materials and Methods. The main source of data used in this study was the mortality sub-register of the population living in territories adjacent to the Semipalatinsk Nuclear Test Site (SNTS). The main study group included residents of the Abay District (n = 1300) and Beskaragay District (n = 414). In total, 478 residents of the Kokpekty District, where the radiation dose was minimal, were included in the control group. The median effective radiation dose was 864 mSv for the population of the exposed group, whereas in the control group, it was 67 mSv. Results. The highest RR values were observed in the periods 1965–1969 (RR = 6.14; 95% CI: 4.04–9.34) and 1970–1974 (RR = 6.14; 95% CI: 4.19–8.99). Age-standardized mortality rates (ASMR) in the study group were significantly higher than those in the control group. A dose–response relationship was established: with each 10.0 mSv increase in radiation dose, the risk of cancer mortality increased by 0.9% (OR = 1.009; 95% CI: 1.008–1.010; p < 0.001). Conclusions. The obtained results indicate a significant association between long-term exposure to ionizing radiation due to testing at the Semipalatinsk Nuclear Test Site and increased cancer mortality among the population of adjacent territories. Full article

Middle ear neuroendocrine tumours (MeNETs) are rare epithelial neoplasms with neuroendocrine differentiation that pose significant diagnostic and therapeutic challenges. The clinical presentation of MeNETs is often nonspecific and can mimic other middle ear pathologies, such as chronic otitis media, cholesteatoma, or paraganglioma Common symptoms include conductive hearing loss, otalgia, intermittent or persistent tinnitus, ear fullness, and dizziness. We present five patients who underwent surgery in our University Otolaryngology Centre between 2019 and 2025, in whom histopathological examination confirmed the diagnosis of MeNET. Although MeNET is typically considered an indolent tumour, rare cases of locally aggressive behaviour and distant metastases have been reported in the literature. Metastatic potential appears to correlate with histopathological features such as increased mitotic activity, Ki-67 proliferation index > 5%. The treatment of choice for MeNET is surgical resection of the tumour, with the choice of surgical technique depending on the stage of the tumour, its relationship to surrounding anatomical structures, and the possibility of hearing preservation. In our study, we highlighted the importance of radical tumour excision to minimize the risk of recurrence. Given the risk of recurrence and the risk of potential metastases, long-term follow-up is necessary, particularly in patients with advanced-stage tumours. Full article