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Niezróżnicowany nowotwór klatki piersiowej z niedoborem SMARCA4 — charakterystyka kliniczno-patomorfologiczna i przegląd piśmiennictwa
No full textNiezróżnicowany nowotwór klatki piersiowej z niedoborem SMARCA4 (SMARCA4-UT, thoracic SMARCA4-deficient undifferentiated tumour) jest wysoce agresywnym nowotworem, po raz pierwszy opisanym w 2015 roku. Charakteryzuje się mutacjami genu SMARCA4 (BRG1), który odgrywa kluczową rolę w kompleksie SWI/SNF remodelującym chromatynę (BAF). W klatce piersiowej SMARCA4-UT najczęściej rozwija się w śródpiersiu i okolicy wnęki płuca. Ze względu na rzadkie występowanie i cechy morfologiczne przypominające inne nowotwory złośliwe rozpoznanie jest trudne i wymaga wykonania szerokiej diagnostyki immunohistochemicznej, niekiedy również badań z wykorzystaniem technik biologii molekularnej. Kluczowe znaczenie ma współpraca wielospecjalistyczna, korelacja danych klinicznych oraz badań obrazowych i histopatologicznych.
Diagnostyka różnicowa obejmuje przede wszystkim niedrobnokomórkowe raki płuca z niedoborem SMARCA4 (SD-NSCLC, SMARCA4-deficient non-small cell lung carcinoma), a także drobnokomórkowe raki jajnika typu hyperkalcemicznego (SCCOHT, small cell carcinoma of the ovary, hypercalcemic type), złośliwe guzy rabdoidne (MRT, malignant rhabdoid tumors) czy raki linii pośrodkowej z rearanżacją NUTM1. Choroba najczęściej występuje u osób nałogowo palących papierosy (tzw. heavy smokers), w średnim wieku (mediana wieku 48 lat), ze znaczną przewagą mężczyzn. Nowotwór charakteryzuje się bardzo agresywnym przebiegiem.
Mediana czasu całkowitego przeżycia (OS, overall survival) wynosi 4–7 miesięcy. Jak dotąd nie ustalono jednolitego schematu leczenia chorych na SMARCA4-UT. Podejmowane próby terapeutyczne obejmują głównie leczenie neoadjwuantowe oraz złożoną immunoterapię.
Obecnie nadzieje wiąże się z dwoma nowymi lekami celowanymi, ukierunkowanymi na patogenezę SMARCA4-UT — tazemetostatem, selekcyjnym inhibitorem EZH2, oraz LY4050784, inhibitorem BRM (SMARCA2), znajdującym się aktualnie w fazie badań klinicznych, do których można kwalifikować chorych
Microbial dynamics in acne pathogenesis: Exploring the impact of skin and intestinal microbiota
No full textThe skin microbiota is a consortium of microorganisms residing on human skin, which undergoes alterations due to external and internal influences, fostering interindividual variability and microbiota dysbiosis. This study aims to elucidate the impact and role of both skin and intestinal microbiota on acne development. The PubMed and Google Scholar databases were used to write the study, searching for articles from 2013 to 2024 and analyzing them in terms of the topic of the review. Acne vulgaris is a persistent skin ailment marked by various manifestations like comedones, pustules, papules, and cysts, predominantly afflicts teenagers, but is not confined to any specific age group. Its intricate etiopathogenesis involves factors such as heightened sebum production and the proliferation of specific Cutibacterium acnes (C. acnes) strains. It is a dominant bacterium in hair follicles in both healthy and affected individuals, with select phylotypes influencing disease progression. Beyond C. acnes, other microorganisms like Malassezia and Staphylococcus epidermidis (S. epidermidis) may contribute to acne development. The intestinal microflora, less diverse in acne patients, actively participates in pathogenesis, potentially exacerbating inflammation and disease course. The microbiotas of the skin and intestines play a significant role in the pathogenesis of acne through multiple mechanisms, and imbalance of the microbiotas may exacerbate acne
Ruxolitinib in third-line treatment of polycythemia vera: a case report
No full textOpis przypadku: U 50-letniego mężczyzny w 2022 roku zdiagnozowano czerwienicę prawdziwą (PV, polycythemia vera). Początkowe leczenie obejmowało krwioupusty, a następnie hydroksymocznik oraz interferon. Oba leki odstawiono z powodu braku skuteczności lub wystąpienia działań niepożądanych, w tym rozległych owrzodzeń jamy ustnej oraz znacznego wzrostu aktywności enzymów wątrobowych. Wnioski: Wprowadzenie ruksolitynibu jako terapii trzeciej linii umożliwiło uzyskanie trwałej remisji hematologicznej, normalizacji wymiarów śledziony oraz regresji włóknienia szpiku kostnego. Leczenie było dobrze tolerowane — dotychczas nie odnotowano żadnych działań niepożądanych.Case report: A 50-year-old male patient was diagnosed with polycythemia vera (PV) in 2022. Initial management included phlebotomy, followed by hydroxyurea and subsequently interferon. Both agents were discontinued due to either lack of efficacy or treatment-related adverse events, including severe oral ulcers and significant elevation of liver enzymes.
Conclusions: Introduction of ruxolitinib as third-line therapy resulted in sustained hematologic remission, normalization of spleen size, and regression of bone marrow fibrosis. The treatment has been well tolerated, with no adverse effects reported to date
Combination of docetaxel and irinotecan as a second-line treatment of metastatic gastric cancer: a phase II study
Full text linkIntroduction. Gastric cancer is one of the aggressive malignancies that negatively impact the performance status of patients and cause a high incidence of cachexia. Docetaxel and irinotecan have confirmed efficacy in the second-line treatment of metastatic patients. However, most patients are not fit enough for third-line options. So, we tested the combination of these two drugs in second-line treatment to give patients the maximum benefit as a “last resort” treatment option.
Material and methods. Prospective analysis of metastatic gastric cancer patients was done in the second-line treatment. Patients received a combination of docetaxel and irinotecan. To assess response, we used RECIST version 1.1; toxicity was assessed with CTCAE version 5.0, quality of life was assessed by the QLQ-C30 model, and survival analysis was done by the Kaplan-Meier curves.
Results. A total of 32 patients were eligible for statistical analysis. The mean age at diagnosis was 56 years. The clinical control rate was 21.8%, of which 12.5% of patients had a partial response and 9.3% had stationary disease. The most common toxicity was neutropenia (18.8%) despite the routine use of prophylactic filgrastim. The median overall survival was 14 months; of which, 9 months represented median progression-free survival 1 (PFS1) and 12.5 months for progression-free survival 2 (PFS2). Reduction in tumor markers CEA and CA19-9 were predictive factors of survival (p = 0.004 and 0.028 respectively). Quality of life was negatively impacted both in responders and non-responders.
Conclusions. The combination of docetaxel and irinotecan is a valid choice for second-line treatment of gastric cancer, especially when carefully selecting suitable patients. This regimen serves as a “last resort” for individuals whose subsequent treatment options primarily involve best supportive care. The study is especially important for countries that do not have access to the recently approved immunotherapy options in this setting
Navigating through unusual — esophageal spindle cell carcinoma
Full text linkIntroduction. Esophageal spindle cell carcinoma is a rare neoplasm of esophagus with unique presentation having varying clinical, histopathological, radiological, and molecular features. It has dual nature of histology consisting of epithelial and sarcomatous components present within the tumor cells. High recurrences are noted in lymph nodes following surgery. Here we report an unusual case of spindle cell carcinoma of middle thoracic esophagus treated with radiation and chemotherapy.
Case report. A 47-years-old adult male presented to Radiation Oncology outpatient department with complains of progressive dysphagia of 2-month duration, associated with hoarseness of voice and weight loss. Contrast enhanced computed tomography showed esophageal thickening and growth in the middle thoracic region. Histopathological examination of growth confirmed esophageal spindle cell carcinoma with vimentin and cytokeratin positivity. Patient underwent external beam radiation therapy followed by salvage oral metronomic chemotherapy. After 2-months of oral chemotherapy, patient lost to follow up.
Conclusions. Spindle cell carcinoma is uncommon malignancy of esophagus, owing to their dual nature of histology within tumor tissue. Patients tend to present with early symptoms. Surgery remains important intervention in management of spindle cell carcinoma. However, lack of uniform consensus underscores the complete management of these uncommon neoplasms. Through this case report and short review, we aim to contribute in establishing uniform consensus
Combination therapies in the treatment of prostate cancer
No full textIn recent years, the therapeutic landscape of prostate cancer has transformed significantly, moving beyond single-agent approaches to employ combination therapies that maximize synergistic effects for enhanced patient outcomes. Since the introduction of docetaxel for metastatic castration-resistant prostate cancer (mCRPC), treatment options have expanded to include androgen receptor pathway inhibitors (ARPI), radioisotope therapies, PARP inhibitors, and cytotoxic agents, collectively improving survival and quality of life across prostate cancer stages. Combination strategies, particularly those integrating ARPI with chemotherapy or PARP inhibitors, have demonstrated significant clinical activity, especially in high-risk metastatic castration-sensitive (mHSPC) and BRCA1/2-mutated mCRPC patients. Clinical trials, such as PEACE-1 and ARASENS, reveal substantial survival benefits for three-drug regimens (ADT, docetaxel, and ARPI) in high-volume mCSPC. In mCRPC, the combination of ARPI and PARP inhibitors leverages synthetic lethality, notably enhancing outcomes in patients with DNA repair deficiencies. Additionally, emerging combinations with radioisotopes, ARPI and chemotherapy provide new avenues for cancer control, highlighting manageable toxicity profiles that facilitate broader patient applicability. However, the limited efficacy of immune checkpoint inhibitors, even in combination settings, underscores the need for tailored combinations based on prostate cancer’s unique molecular profile. This review synthesizes the latest evidence on combined systemic therapies in prostate cancer, underscoring the importance of strategically pairing agents to exploit distinct mechanisms of action while maintaining a favorable safety profile. The evolving model of combination therapy in prostate cancer presents promising insights for similar approaches in other solid tumors, marking a pivotal shift in oncological treatment paradigms
Encorafenib with binimetinib efficacy in the first, second, and third line of treatment for patients with advanced melanoma harboring a BRAF mutation — real-world study
No full textIntroduction. In patients with advanced melanoma with BRAF mutation, the BRAF and MEK inhibitors can be used before or after immunotherapy, and even as third-line systemic treatment. To date, majority of available data on encorafenib plus binimetinib comes from clinical trials.
Material and methods. This was a multicenter retrospective study, which aimed to investigate the efficacy of encorafenib plus binimetinib (E+B) treatment in patients with unresectable stage III or IV melanoma in the real-world setting. The study did not include patients treated with adjuvant intent. Progression-free survival (PFS) and overall survival (OS) estimates were obtained using Kaplan–Meier method.
Results. There were 130 patients treated in the first-line setting. Their median follow-up was 24.1 (95% CI 20.9–32) months. Median age of the group treated with E+B first line treatment was 63.5 years and LDH level was abnormal in 53.1% of cases, while 25.4% of patients had brain metastases. The median PFS was 10.3 (95% CI 8–12.4) months, 1- and 3-year PFSs were 40.1% (95% CI 31.9–50.3) and 12.3% (95% CI 6.1–24.7), while the objective response rate (ORR) was 58.5%. After the progression of the disease, 32 (24.6%) patients received second-line treatment (including immunotherapy in 28, 87.5% cases) and 5 (3.8%) patients received third-line treatment. The median OS from the start of the first-line treatment was 15.8 (95% CI 12–23.5) months, while the 1-year and 3-year OS rates were 58% (95% CI 49.6–67.9) and 20% (95% CI 11.9–33.6), respectively. In the second-line treatment, after the anti-PD-1-based first-line treatment, the E+B was administered in 82 patients. The median PFS was 8.5 (95% CI 6.5–12) months, and the ORR was 42 (51.2%). The median OS from the start of the second-line treatment was 13.2 (95% CI 10.9–22) months. In the third-line treatment, E+B was used in 23 patients, with 6- and 12-month PFS being 23% (95% CI 10.7–49.6), and 13.8% (95% CI 4.8–39.4), respectively. The median PFS in third-line setting was 3.6 (95% CI 2.8–5.3) months.
Conclusions. This real-world evidence supports the clinically meaningful efficacy of the combination of E+B in first-, second- and third-line treatment
