Onkologijos ir hematologijos klinika (K330000)

Background and Objectives: Rectal cancer management has changed substantially over the past two decades. We evaluated 20-year trends in stage at diagnosis, treatment patterns, and survival at a Lithuanian tertiary referral centre. Materials and Methods: This retrospective cohort study included 839 patients who underwent resection for stage I–III rectal cancer between 2004 and 2023, divided into two periods: 2004–2013 (n = 426) and 2014–2023 (n = 413). Survival was analysed with Kaplan–Meier estimates and Cox proportional hazards regression, truncated at 60 months. Results: Patients in the later cohort were diagnosed at an earlier clinical stage (stage I: 12.6% vs. 2.4%) and more often received neoadjuvant or perioperative therapy (55.2% vs. 37.1%; p < 0.001). Among clinical stage III patients, receipt of neoadjuvant chemoradiotherapy or total neoadjuvant treatment rose from 15.9% to 70.9% (p < 0.001), while pathological complete response among treated patients remained stable (10.8% vs. 10.7%; p = 0.98). Five-year overall survival increased from 64.8% to 71.3% (HR 0.77; 95% CI 0.60–0.99; p = 0.039) and cancer-specific survival from 70.4% to 80.8% (HR 0.60; 95% CI 0.45–0.80; p = 0.0005). The cohort effect persisted after multivariable adjustment for CSS (HR 0.62; 95% CI 0.45–0.85; p = 0.003), with clinical stage explaining only ~13% of the crude effect; stage III sensitivity analysis confirmed the CSS gain (67.9% to 77.3%; p = 0.009). Conclusions: Cancer-specific survival improved substantially and independently of stage migration. The gain coincided with markedly wider and better-targeted delivery of effective neoadjuvant therapy rather than with improved per-patient tumour responsiveness. As an observational comparison of two historical cohorts, this study demonstrates association rather than causation; nonetheless, it provides real-world evidence consistent with the hypothesis that systematic implementation of evidence-based rectal cancer pathways translates into measurable survival benefit.

Įvadas. Hormonų receptorių teigiama (HR+) ir nepadidėjusios žmogaus epidermio augimo faktoriaus receptoriaus 2 raiškos (HER2-) karcinoma yra dažniausias krūties vėžio potipis [...].

Introduction: Hematopoietic stem cell transplantation (HSCT) is an effective treatment option for haematological malignancies (HM), although it involves potentially cardiotoxic therapies. Cardiotoxicity is currently defined mainly by reduction in left ventricular ejection fraction (LVEF) and/or global longitudinal strain (GLS), which may occur after earlier subclinical myocardial changes have already developed [1]. While transthoracic echocardiography is the first-line modality, its sensitivity for early subclinical myocardial changes may be limited. Cardiac magnetic resonance (CMR) enables more comprehensive assessment of ventricular function, deformation and geometry, yet data on CMR-detected subclinical myocardial remodelling after HSCT remains limited [2]. Purpose: To evaluate subclinical myocardial remodelling before and one year after HSCT using CMR-derived functional, deformation and geometric parameters. Methods: Thirty-nine patients with HM undergoing HSCT were prospectively enrolled. CMR was performed before HSCT and at one-year follow-up using a 3T scanner. Left ventricular (LV) and right ventricular (RV) volumes, systolic function longitudinal and circumferential strain, ventricular geometry and mitral valve-LV (MV-LV) coupling parameters were assessed. Statistical analysis was performed using IBM SPSS 29.0. Paired comparisons between baseline and one-year follow-up were performed, with correlation and subgroup analyses based on baseline values, sex and age. The study protocol was approved by our Regional Biomedical Research Ethics Committee. Results: The study population had a median age of 61 years (range 18-74). Of the 39 patients included, 21 were men (53.8%) and 18 were women (46.2%). LVEF, LV geometry, volumes, GLS and circumferential strain did not change significantly. MV-LV coupling analysis demonstrated an increase in MV end-systolic area (p=0.015) and a greater systolic circumferential strain dispersion at the mitral level (p=0.021). Overall mitral annular circumferential strain remained unchanged, but patients with worse baseline values exhibited significantly greater deterioration (p=0.033), indicating heterogeneous MV-LV coupling response. RV remodelling was characterized by a deterioration in RV GLS (p=0.023) and an increase in RV ESL (p=0.039), with basal diameter changes affecting patients with smaller baseline values (p=0.005). Changes in mitral annular circumferential strain correlated with changes in RV GLS (ρ=0.727, p<0.001). Increasing age was associated with greater LV GLS deterioration over time (ρ=0.54, p<0.001). Conclusions: Despite preserved ventricular volumes and global systolic function, CMR revealed early and heterogeneous subclinical myocardial remodelling one year after HSCT, involving MV-LV coupling and RV function. These findings suggest selective vulnerability of myocardial mechanics not detected by conventional functional parameters.

Introduction Radiotherapy is a vital therapeutic option in the treatment of breast cancer nowadays. However, a major obstacle to the full effectiveness of radiation therapy is still the radioresistance of cancer cells. Various studies have proven sulforaphane's (SFN) beneficial effects against cancer and its possible utilization as a radiosensitizer in radiotherapy. This study aimed to investigate whether SFN has a radiosensitizing effect on breast cancer cells.

Material and methods The anticancer efficiency of SFN and radiosensitizing effect in MCF-7 and MDA-MB-231 cell lines were assessed by the MTT assay. Using a flow cytometric assay, the apoptosis level and changes in the cell cycle were measured. RT-qPCR and Western blot analysis were used to determine BCL-2 and BCL-XL genes expresion and proteins level.

Results According to our results, SFN reduced the viability of cells, and combining SFN with radiation therapy (IR) caused much greater anticancer effects on cells. SFN+IR was shown to enhance the number of cells in the G2/M phase and the percentage of cells going through apoptosis. SFN reduced the expression of apoptosis-relative genes BCL-2 and BCL-XL. Consistent with this data, Western blot analysis revealed that BCL-2 and BCL-XL protein levels were decreased in tested cells. As a result of the combination treatment, the downregulation of the BCL-2 protein was observed only in MDA-MB-231 cells.

Conclusions These results indicate that SFN acts as a radiosensitizer by enhancing apoptotic cell death and reducing anti-apoptotic genes in breast cancer cells.

Cancer remains a major health burden in Lithuania, emphasizing the importance of effective undergraduate oncology education. This paper describes the structure and key features of the integrated oncology curriculum at the Lithuanian University of Health Sciences (LSMU). Oncology teaching is embedded within a six-year medical programme, combining early exposure through biomedical sciences with focused clinical training in a mandatory Year IV Hematology and Oncology module. Teaching methods include lectures, small-group seminars, and supervised ward-based learning, with a strong emphasis on case-based discussion and clinical reasoning. Students are introduced to principles of cancer diagnosis, staging, treatment, and multidisciplinary decision-making. Simulation and practical skills training further support clinical competence. Assessment includes written examinations and clinical case assignments, aligned with programme-level evaluations such as OSCE. Teaching is delivered in a multidisciplinary academic environment with structured quality assurance and continuous student feedback. This model provides a clinically grounded and integrated approach to cancer education, ensuring continuity from undergraduate medical education to postgraduate specialist training. Expanding hands-on clinical exposure, strengthening communication training, and incorporating emerging technologies such as artificial intelligence may further enhance the curriculum.

Background: Toxic epidermal necrolysis (TEN) is a rare but life-threatening complication that may occur in patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT), particularly in the context of extensive drug exposure. In this population, TEN can closely resemble severe acute graft-versus-host disease (GVHD), making diagnosis and management challenging. Case presentation: We report the clinical course of an allo-HSCT recipient who developed a rapidly progressive skin rash early after transplantation, and we analyzed the clinical features, histopathology, treatment and outcome. Results: The patient developed rapidly progressive epidermal detachment with severe oral, ocular, and genital mucosal involvement shortly after exposure to trimethoprim/sulfamethoxazole (TMP-SMX). Disease severity was reflected by a SCORTEN score of 5, corresponding to a very high predicted mortality risk. The clinical picture raised concern for both TEN and severe acute GVHD, while histopathological findings favored TEN but were not definitive. Management included systemic corticosteroids, intravenous immunoglobulin, ruxolitinib, and intensive supportive care. The patient gradually re-epithelialized and recovered without long-term sequelae. Conclusions: This case underscores the diagnostic difficulty of distinguishing TEN from severe acute GVHD in the early post-transplant period. Careful assessment of drug exposure, clinical evolution, and multidisciplinary evaluation are essential to guide timely and appropriate management.

The field of oncology has witnessed remarkable progress with the integration of high-tech innovations in tumor ablation. Tumor ablation therapies, such as radiofrequency ablation (RFA), microwave ablation (MWA), cryoablation (Cryo), irreversible electroporation (IRE), and electrochemotherapy (ECT) have evolved beyond conventional boundaries, offering patients less invasive, highly targeted therapeutic options. Since it works across cancer histologies, tumor ablation is being integrated into cancer care at several levels. Tumor ablation is even considered curative in selected patients with small primary or secondary tumors, e.g. in the liver. Furthermore, it is central in treatment of oligometastatic disease or oligoprogression. Finally, ablation is widely used for symptomatic relief when tumors lead to symptoms affecting quality of life. Knowledge about ablative therapies and their inclusion at multidisciplinary team decision making enables effective and more personalized treatment for patients. This review synthesizes emerging applications of these therapies, focusing on artificial intelligence-driven personalization, robotic-assisted precision, and hybrid models combining ablation with systemic treatments, immunotherapy or targeted drug delivery. It also discusses the infrastructural, educational, regulatory, and ethical challenges that influence the clinical adoption of such treatments. Finally, the review presents strategic recommendations for integrating advanced ablation therapies into healthcare systems while ensuring equity, patient trust, and global accessibility.

Introduction and Aim The 2022 World Health Organization (WHO) classification recognizes myeloid neoplasms with germline predisposition as a distinct clinical entity. Pathogenic variants in the DDX41 gene are the most frequent cause of hereditary predisposition to myeloid malignancies in adults. These cases typically follow a "two-hit" molecular model: a germline mutation followed by an acquired somatic mutation. The aim of this report is to describe the clinical and molecular evolution of a patient with bi-allelic DDX41 mutations and to emphasize the role of next-generation sequencing (NGS) in differentiating germline from somatic variants. Case report The patient is a 56 year old male who was diagnosed with myelodysplastic neoplasm with increased blasts (MDS-IB2) following the detection of macrocytic anemia and severe neutropenia (ANC 0.48 x 109/l) in November 2024. Two targeted short-read NGS analyses using a myeloid gene panel were performed to monitor clonal evolution: at diagnosis (2024-11-18) and after treatment (2025-05-20) using DNA extracted from bone marrow at both time points. Initial NGS revealed two DDX41 variants: c.3G>A (p.Met1?) with a variant allele frequency (VAF) of 43.87% and c.1574G>A (p.Arg525His) with a VAF of 9.14%. Additional somatic mutations were identified in CUX1 (c.766C>T, VAF 5.29%) and CBL (c.1202G>A, VAF 4.31%). Following diagnosis, treatment was initiated, the patient completed a total of six cycles of Azacitidine. Follow-up NGS showed that the c.3G>A variant remained stable (VAF 42.91%), while the somatic DDX41 p.Arg525His mutation decreased to 4.12%. Reductions were also noted in the CUX1 (VAF 2.31%) and CBL (VAF 2.06%) mutations. Despite intermittent infectious complications, the patient’s clinical status remains stable (ECOG 0). Discussion The stability of the DDX41 c.3G>A variant at a VAF near 50% across both time points strongly suggests a germline origin, whereas the significant reduction in the p.Arg525His variant indicates a molecular response of the malignant clone to hypomethylating therapy. The presence of the p.Arg525His mutation is a classic somatic "second hit" in DDX41-related neoplasms. Identifying this germline predisposition is vital because it necessitates family screening and dictates a strict donor selection algorithm for allogeneic hematopoietic stem cell transplantation to avoid the risk of donor-derived leukemia. Conclusions Dynamic NGS monitoring is an essential tool for differentiating germline predisposition from somatic clonal evolution in myeloid neoplasms. In DDX41- mutated MDS, recognizing the underlying genetic predisposition is critical for accurate prognosis, clinical management, and the safety of family-based stem cell donation.

Introduction and Aim Electrochemotherapy (ECT) is a local treatment modality that combines electrical pulses with cytotoxic drugs, most commonly bleomycin and cisplatin. Electrical pulses induce reversible electroporation, increasing cell membrane permeability and enhancing drug uptake into tumour cells. In addition, a “vascular lock” effect is induced, causing transient vasoconstriction that prolongs drug retention within the tumour and enhances its cytotoxic effect. ECT is widely used for the management of cutaneous and subcutaneous metastases. Breast cancer represents one of the most common indications due to the high incidence of skin metastases in advanced disease. Since February 2024, this procedure has been implemented in clinical practice at the Hospital of the Lithuanian University of Health Sciences Kauno Klinikos, Department of Oncology and Haematology. This enables the use of ECT as an additional method of local disease control in routine clinical settings, providing patients with an additional therapeutic option, particularly in cases where the effectiveness of systemic treatment is limited. The effectiveness and feasibility of this approach are further supported by the three clinical cases presented. Case report 1 A 57-year-old female with right-sided invasive ductal carcinoma of the breast (G3, ER+, PR+, HER2 (1+)) and a confirmed pathogenic BRCA2 mutation presented with an approximately 3 cm erythematous area in the mastectomy scar region following multimodal treatment. Clinical examination revealed several small palpable infiltrative lesions consistent with cutaneous metastases. Due to locally progressive skin disease, ECT with intravenous bleomycin was performed, resulting in regression of cutaneous lesions, with lightening of nodules and no development of new lesions. Case report 2 A 71-year-old female with left-sided invasive ductal carcinoma of the breast (G2, triplenegative subtype) presented with disease progression despite multimodal treatment, including the development of liver and cutaneous metastases. Due to symptomatic and progressive skin lesions, ECT with intravenous bleomycin was performed. ECT was repeated twice to maintain local disease control. Case report 3 A 46-year-old female with right-sided invasive ductal carcinoma of the breast, characterized by an aggressive and progressive course. During the disease course, cutaneous, lymph node, pulmonary, and hepatic metastases developed. The disease was refractory to multiple lines of systemic therapy, including chemotherapy and immunotherapy. Due to extensive cutaneous involvement, ECT with intravenous bleomycin was performed repeatedly (four treatment sessions in total), achieving local control of cutaneous lesions. Discussion Cutaneous metastases are often inadequately controlled by conventional systemic therapy due to limited drug penetration associated with poor tumour perfusion, increased interstitial pressure, and a complex tumour microenvironment, as well as tumour heterogeneity and acquired resistance. Electrochemotherapy, by combining electroporation with cytotoxic agents, significantly enhances intracellular drug uptake and enables effective local tumour control, even in cases refractory to systemic treatment. Importantly, ECT should not be considered a standard systemic treatment modality, but rather a valuable additional therapeutic option for selected patients requiring local disease control. Previous studies have shown that electrochemotherapy achieves an overall response rate of 60–80% in the treatment of cutaneous metastases, with complete response rates of up to 40–50%. The method is safe, well tolerated, and can be repeated when necessary. Breast cancer is one of the most frequent indications for ECT due to its tendency to metastasize to the skin of the chest wall. In the presented cases, ECT enabled effective local control of lesions, reduced symptoms, and improved quality of life, regardless of tumour biological subtype. However, ECT has no significant impact on systemic disease and should therefore be applied as part of a multidisciplinary treatment approach. Conclusions Electrochemotherapy is an effective and safe method for the treatment of cutaneous metastases of breast cancer. It should be considered in patients requiring local disease control, particularly in cases of limited systemic treatment options or progression of disease in the skin.

Background and Objectives CMV infection remains a common and clinically significant complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT), particularly in the setting of profound post-transplant immunosuppression. CMV reactivation occurs frequently in the early post-transplant period and represents a major challenge in clinical management, especially among seropositive recipients. It may contribute not only to direct organ involvement but also to indirect effects, including increased susceptibility to secondary infections and impaired immune reconstitution. The clinical impact of CMV reactivation may vary depending on patient-related and transplantrelated factors, reflecting the heterogeneity of the transplanted population. Despite advances in viral monitoring and preemptive therapy, CMV reactivation continues to be associated with an increased risk of post-transplant complications and higher mortality rates. This study aimed to assess the frequency of CMV reactivation and evaluate its impact on complications and early post-transplant mortality in a retrospective single-center cohort. Material and Method A retrospective single-center study was conducted including 77 patients who underwent allogeneic hematopoietic stem cell transplantation at the Hospital of Lithuanian University of Health Sciences Kaunas Clinics between 2020 and 2025. The study population consisted of adult patients with a median age of 56 years, with a balanced sex distribution, and predominantly myeloid underlying diseases. CMV reactivation was monitored using quantitative polymerase chain reaction. Associations between CMV reactivation and post-transplant complications as well as early posttransplant mortality were analyzed using appropriate statistical methods, including chisquare or Fisher’s exact test for categorical variables and non-parametric tests for continuous variables. Early mortality was defined as death during the initial posttransplant hospitalization or within 100 days after transplantation, whichever occurred later. Multivariate logistic regression analysis was performed to identify independent risk factors. IBM SPSS Statistics (version 30.0.0) was used for statistical analysis. A p-value < 0.05 was considered statistically significant. Results CMV reactivation was observed in 53.2% of patients and occurred in 58.0% of seropositive recipients with available serostatus data. The median time to CMV reactivation was 14 days after transplantation (IQR 7.5–27.5), with a mean of 17.8 ± 12.0 days. Antiviral treatment for CMV infection was required in 43.9% of patients with reactivation, reflecting a substantial clinical burden of CMV management after transplantation. CMV reactivation was more frequently observed in patients who developed graft-versus-host disease (65.0% vs. 49.1%), although this difference did not reach statistical significance. Patients with CMV reactivation had a higher frequency of infectious complications (70.7% vs. 55.6%) and overall complications (85.4% vs. 72.2%) compared to those without reactivation; however, these associations did not reach statistical significance. A similar trend was observed across different complication types, suggesting a consistent pattern despite the lack of statistical significance. No significant association was found between CMV DNA load and the number of complications; however, this finding should be interpreted with caution given the limited sample size. CMV reactivation was associated with significantly increased early post-transplant mortality (36.6% vs. 11.1%; p = 0.010), indicating a clinically meaningful impact on early outcomes. In multivariate analysis adjusted for age and graft-versus-host disease, CMV reactivation remained an independent predictor of early mortality (OR = 5.00; 95% CI: 1.44–17.39; p = 0.011). These findings highlight the clinical relevance of CMV reactivation in the early post-transplant period. Conclusions and Recommendations CMV reactivation is a frequent complication after allo-HSCT and was associated with significantly increased early post-transplant mortality, remaining an independent predictor after adjustment for relevant clinical factors. A consistent trend towards higher rates of infectious and overall complications was observed in patients with CMV reactivation, although statistical significance was not reached. In contrast to findings reported in the literature, no association was identified between CMV DNA load and complication burden, which is likely related to the limited sample size of this study. The relatively small cohort (n = 77) may have reduced the statistical power to detect significant associations. These findings highlight the importance of careful CMV monitoring and timely antiviral intervention in the early post-transplant period. Further studies with larger cohorts are needed to better define the clinical impact of CMV reactivation and to validate these findings.