Cardiotoxicity Induced by Protein Kinase Inhibitors in Patients with Cancer.

Kinase inhibitors (KIs) represent a growing class of drugs directed at various protein kinases and used in the treatment of both solid tumors and hematologic malignancies. It is a heterogeneous group of compounds that are widely applied not only in different types of tumors but also in tumors that are positive for a specific predictive factor. This review summarizes common cardiotoxic effects of KIs, including hypertension, arrhythmias with bradycardia and QTc prolongation, and cardiomyopathy that can lead to heart failure, as well as less common effects such as fluid retention, ischemic heart disease, and elevated risk of thromboembolic events. The guidelines for cardiac monitoring and management of the most common cardiotoxic effects of protein KIs are discussed. Potential signaling pathways affected by KIs and likely contributing to cardiac damage are also described. Finally, the need for further research into the molecular mechanisms underlying the cardiovascular toxicity of these drugs is indicated.

Effects of Transcutaneous Electrical Nerve Stimulation on Pain and Chemotherapy-Induced Peripheral Neuropathy in Cancer Patients: A Systematic Review.

Transcutaneous electrical nerve stimulation (TENS) is the usage of a mild electrical current through electrodes that stimulate nerves. Patients with malignancies experience pain and chemotherapy-induced peripheral neuropathy. A systematic review was performed to find research evaluating the effect of TENS on these two common symptoms decreasing the quality of life in cancer patients. PubMed, the Cochrane Central Register of Controlled Trials and EMBASE were searched. Original studies, namely randomized controlled trials, quasi-randomized controlled trials and controlled clinical trials, published between April 2007 and May 2020, were considered. The quality of the selected studies was assessed. Seven papers were incorporated in a qualitative synthesis, with 260 patients in total. The studies varied in terms of design, populations, endpoints, quality, treatment duration, procedures and follow-up period. Based on the results, no strict recommendations concerning TENS usage in the cancer patient population could be issued. However, the existing evidence allows us to state that TENS is a safe procedure that may be self-administered by the patients with malignancy in an attempt to relieve different types of pain. There is a need for multi-center, randomized clinical trials with a good methodological design and adequate sample size.

Medical students' perception of e-learning approach (MeSPeLA) - a mixed method research.

There is a discrepancy between the research exploring e-learning at medical universities in Central/Eastern and Western European countries. The aim of the MeSPeLA study was to explore the understanding, experience and expectations of Polish medical students in terms of e-learning. Questionnaire containing open-ended and closed questions supplemented by focus group discussion was validated and performed among 204 medical students in Poland before COVID-19 pandemia. Several domains: understanding of e-learning definitions; students' experience, preferences, expectations and perceptions of e-learning usefulness, advantages and disadvantages were addressed. The qualitative data were analyzed using an inductive approach. 46.0% of students chose a communication-oriented definition as the most appropriate. 7.4% claimed not to have any experience with e-learning. 76.8% of respondents indicated they had contact with e-learning. The main reported e-learning advantages were time saving and easier time management. The most common drawback was limited social interactions. The acceptance of the usage of e-learning was high. Medical undergraduates in Poland regardless of the year of studies, gender or choice of future specialization showed positive attitudes towards e-learning. Students with advanced IT skills showed a better understanding of the e-learning definition and perceived e-learning to be a more useful approach. The expectations and perceptions about e-learning in Polish medical schools seems similar to some extent to that in Western European and the United States so we can be more confident about applying some lessons from these research to Poland or other post-communist countries. Such application has been accelerated due to COVID-19 pandemia.

Primary cardiac atrial sarcomas. Report of two histologically different cases and review of the literature.

Primary cardiac sarcomas are extremely uncommon. We report two patients with primary cardiac atrial sarcomas: a case report of a 34-year old woman with intimal sarcoma of the left atrium and a case report of a 30-year old man with synovial sarcoma of the right atrium. Clinicopathological and differential diagnosis with a discussion regarding the role of molecular studies is presented.

Acupuncture: could it become everyday practice in oncology?

Acupuncture is a complementary and alternative medical treatment (CAM) which is increasingly used in the care of cancer patients. Traditionally derived from Chinese medicine, nowadays it is becoming a part of evidence-based oncology. The use of acupuncture in these patients has been recommended by the American Cancer Society (ACS) for the treatment of side effects associated with conventional cancer therapy and cancer-related ailments. A growing body of evidence supports the use of acupuncture in the treatment of cancer-induced pain and chemotherapy-related nausea and vomiting. Also other indications, such as xerostomia, fatigue, hot flashes, anxiety and peripheral neuropathy, are being constantly evaluated. This article summarizes the most important discoveries related to the possible usefulness of this method in contemporary oncology. Emphasis is placed on the results of randomized controlled trials with an adequate level of evidence. However, explanation of the mechanisms responsible for these effects requires confirmation in further studies with an adequate level of evidence. In future, acupuncture may become an interesting and valuable addition to conventional medicine.

Acupuncture as anticancer treatment?

The mystery of Traditional Chinese Medicine has been attracting people for years. Acupuncture, ranked among the most common services of Complementary and Alternative Medicine, has recently gained a lot of interest in the scientific world. Contemporary researchers have been continuously trying to shed light on its possible mechanism of action in human organism. Numerous studies pertaining to acupuncture's application in cancer symptoms or treatment-related side effects management have already been published. Moreover, since the modern idea of acupuncture's immunomodulating effect seems to be promising, scientists have propounded a concept of its potential application as part of direct anti-tumor therapy. In our previous study we summarized possible use of acupuncture in management of cancer symptoms and treatment-related ailments, such as chemotherapy-induced nausea and vomiting, pain, xerostomia, vasomotor symptoms, neutropenia, fatigue, anxiety, insomnia, lymphoedema after mastectomy and peripheral neuropathy. This article reviews the studies concerning acupuncture as a possible tool in modern anticancer treatment.

Synchronous extraskeletal Ewing's sarcoma/PNET and gallbladder carcinoma: a case report and literature review.

Ewing's sarcoma (ES) and primitive neuroectodermal tumour (PNET) are now considered to be the same tumour and usually occur in long bones. Extraskeletal Ewing's sarcoma is an extremely rare neoplasm, accounting for 1% of soft tissue sarcomas, with most common location in the thorax. Gallbladder cancer (GBC) represents the most common type among the biliary tract cancers with a poor prognosis even among patients undergoing aggressive therapy. We present study of extraskeletal ES/PNET found in the hilus of the liver of an elderly, diagnosed one month prior with GBC woman. The patient underwent two cycles of chemotherapy SAIME/SAVAC for ES and thereafter was operated. During three-year follow-up no recurrence of ES/PNET has been reported. However, two years after chemotherapy the patient suffered a relapse of adenocarcinoma of the gallbladder and thus received palliative chemotherapy of gemcitabine and cisplatin. After 16 months of recurrence she died. To the best of our knowledge, this is the first case of ES/PNET located in the hilus of the liver and as a synchronous neoplasm.

Adenoid cystic carcinoma of the external auditory canal with metastases to lymph nodes and lungs--problematic diagnosis and treatment based on a case report.

Adenoid cystic carcinoma (ACC) of the external auditory canal (EAC) is an exceedingly rare tumor. Despite the slow growth it is characterized by a high malignancy and infiltration of surrounding tissue. Differential diagnosis may be especially difficult if the tumor appears in an atypical localization as it can present with non-specific features. The optimal treatment of this malignancy has not been fully established. We present a case report of a 55-year-old man with ACC of EAC metastasizing to the lymph nodes, lungs and vertebrae, with intracranial involvement. The patient was initially diagnosed with basal cell carcinoma (BCC) of EAC based on MR imaging examinations and excisional biopsy from EAC. Current information about nomenclature, epidemiology, characteristic features and treatment possibilities of ACC are presented and difficulties in making diagnosis are discussed. ACC should be considered among the malignant tumors of EAC. Its natural behavior is probably more unpredictable than commonly thought. Similar cases are rare and our knowledge about the tumor's specificity and prognosis is limited.

Validation of the Polish version of the EORTC QLQ-BM22 module for the assessment of health-related quality of life in patients with bone metastases.

PURPOSE: The aim of our study was to undertake a prospective validation study of the Polish version of the European Organization for Research and Treatment of Cancer (EORTC) bone metastases (QLQ-BM22) module used alongside the EORTC core measure. METHODS: The translated module was pilot-tested according to the established EORTC guidelines. Patients with histological confirmation of malignancy and bone metastases, diagnosed by imaging studies, were eligible for the study. All patients filled out the Polish version of the QLQ-BM22 module in addition to QLQ-C30 and a demographic questionnaire. Standard validity and reliability analyses were performed. RESULTS: One hundred and fifty-five patients were enrolled into the study, including 94 women (60.7 %) and 61 men (mean age ± SD; 59.1 ± 12.1). Cronbach's alpha coefficients, range 0.68-0.93, showed positive internal consistency. Re-test was undertaken with fifty patients (32.3 %). Interclass correlations for the EORTC QLQ-BM22 ranged from 0.91 to 0.93 and proved sufficient test-retest reliability. Satisfactory convergent and discriminant validity in multi-trait scaling analyses was seen. CONCLUSIONS: Our study provides new and robust evidence which shows that the Polish version of the QLQ-BM22 module is a valid and reliable instrument for measuring health-related quality of life in patients with bone metastases. It is suitable for use in clinical trials and in research.

Serum potassium, sodium and calcium levels in healthy individuals - literature review and data analysis.

PURPOSE: The human body is known to be composed of 24 elements, among which potassium, sodium and calcium are considered to be essential. These necessary components play a significant physiological role which includes regulation of the electrical and mechanical action of the heart. Abnormal concentration of the above-mentioned ions, i.e. water-electrolyte imbalance, may result in cardiac arrhythmias, muscle contraction disorders, disturbances of neuronal activity and influences the drugs activity. METHODS: The study aimed at gathering and analyzing results of publicly available research which reported serum concentration of these ions. This information, together with an additional collection of data (gender, age, height, weight, measurement method), is presented in table form attached as supplementary material. RESULTS: The serum ions concentrations means weighted by the study-specific sample sizes indicated statistically significant differences between males and females for all ions - K+ 4.21 and 4.09, Na+ 140.1 and 138.17, Ca2+ 2.42 and 2.31 respectively). CONCLUSIONS: Obtained results correspond with the current laboratory reference values. As potassium, sodium and calcium follow the circadian rhythm, publications reporting serum concentration values were also collected and presented. Further studies are planned to describe such phenomenon in a form of the statistical model.

Oncological emergencies: increased intracranial pressure in solid tumours' metastatic brain disease.

Increased intracranial pressure due to metastatic brain disease is one of the oncological emergencies. It may cause herniation or insufficient brain blood flow, thus it is a life-threatening condition. This article focuses on diagnostic and treatment options, which should be introduced immediately. The prognosis remains poor.

Oncological emergencies: superior vena cava syndrome.

Superior vena cava obstruction leads to the venous hypertension of the head, neck, upper extremities and upper part of the truncus. Its clinical manifestation, known as the superior vena cava syndrome, is a complication of malignancy, mainly of lung cancer and lymphoma. As it usually affects patients with advanced disease, the prognosis is poor. This article stresses the importance of early detection and adequate management of this onco- logical emergency. The diagnostic tools as well as treatment possibilities are discussed.

Oncological emergencies: syndrome of inappropriate antidiuretic hormone secretion (SIADH).

Excessive secretion of vasopressin in the course of Syndrome of Inappropriate Antidiuretic Hormone Secretion is a common cause of hyponatremia in cancer patients. Clinical symptoms depend on the cause, rate of change of sodium level and their absolute values. Treatment options include fluid restrictions, intravenous administration of hypertonic sodium chloride solutions, loop diuretics and vaptans. The sodium level should not be adjusted too fast, because it may lead to irreversible brain damage. The article presents pathophysiology, diagnostics and recommendations of management of this oncological emergency.

The therapeutic potential of natural metabolites in targeting endocrine-independent HER-2-negative breast cancer.

Breast cancer (BC) is a heterogenous disease, with prognosis and treatment options depending on Estrogen, Progesterone receptor, and Human Epidermal Growth Factor Receptor-2 (HER-2) status. HER-2 negative, endocrine-independent BC presents a significant clinical challenge with limited treatment options. To date, promising strategies like immune checkpoint inhibitors have not yielded breakthroughs in patient prognosis. Despite being considered archaic, agents derived from natural sources, mainly plants, remain backbone of current treatment. In this context, we critically analyze novel naturally-derived drug candidates, elucidate their intricate mechanisms of action, and evaluate their pre-clinical in vitro and in vivo activity in endocrine-independent HER-2 negative BC. Since pre-clinical research success often does not directly correlate with drug approval, we focus on ongoing clinical trials to uncover current trends. Finally, we demonstrate the potential of combining cutting-edge technologies, such as antibody-drug conjugates or nanomedicine, with naturally-derived agents, offering new opportunities that utilize both traditional cytotoxic agents and new metabolites.

Immunotherapy in MMR-d/MSI-H recurrent/metastatic endometrial cancer.

INTRODUCTION: The advent of immunotherapy with immune checkpoint inhibitors (ICIs) has revolutionized the management of mismatch repair deficient (MMR-d)/microsatellite instability-high (MSI-H) endometrial cancer (EC). Initially investigated as monotherapy in phase I-II clinical trials for recurrent disease, immunotherapy demonstrated remarkable activity, yielding overall response rates (ORR) ranging from 27% to 58%. Based on these promising findings, phase III trials have explored the integration of immunotherapy into first-line treatment regimens for advanced/recurrent EC in combination with chemotherapy or other agents such as tyrosine kinase inhibitors (TKIs), resulting in improved ORR, progression-free survival, and overall survival compared to the standard chemotherapy regimen of paclitaxel and carboplatin. As a result, the incorporation of ICIs with standard platinum-based chemotherapy is becoming a new standard of care in MMR-d/MSI-H EC. AREAS COVERED: This review synthesizes literature from PubMed, Embase databases, and recent congress abstracts on gynecological cancers. It covers MMR-d/MSI-H EC incidence, molecular diagnostics, clinical trial outcomes, predictive biomarkers for ICIs, patient profiles likely to benefit, resistance mechanisms, and the future of immunotherapy in this setting. EXPERT OPINION: By offering a comprehensive overview, this review delineates the pivotal role of ICIs in the management of MMR-d/MSI-H EC.

Cisplatin Monotherapy as a Treatment Option for Patients with HER-2 Negative Breast Cancer Experiencing Hepatic Visceral Crisis or Impending Visceral Crisis.

INTRODUCTION: Hepatic visceral crisis (VC), characterized by a rapid total bilirubin increase with disease progression, poses a life-threatening risk in advanced breast cancer (ABC). International consensus guidelines define VC and touch on impending VC (IVC). Limited data exist on systemic treatments for hepatic VC/IVC. This study explores the safety and efficacy of cisplatin monotherapy in patients with Human Epidermal Growth Factor Receptor 2- negative breast cancer (BC) and hepatic IVC/VC. METHODS: In this retrospective single-center cohort study data of patients treated with cisplatin monotherapy (60-80 mg/m2, every 3-4 weeks) between 2016 and 2023 at a reference Cancer Centre in Southern Poland were analyzed. RESULTS: 33 female patients (24/33 hormonal-positive) with the mean age 53.84 years were included. Participants progressed on median 2 prior palliative systemic treatment lines. In 10/23 patients hepatic VC and in 23/33 IVC (rapid, symptomatic liver progression; extensive liver involvement; alanine or aspartate aminotransferase > 2 × normal limit; significant increases in lactate dehydrogenase, alkaline phosphatase, or gamma-glutamyl transferase) were identified. Median progression-free survival was 1.87 months and median overall survival 2.67 months. 33% of the patients presented stable disease or partial response. Eight patients experienced adverse events grade ≥ 3: in five the dose of cisplatin was reduced; two stopped the treatment. CONCLUSION: Due to the hepatotoxicity of BC-active drugs, specific recommendations for systemic treatment are scarce. Our study explored cisplatin's potential use, finding it to be a viable option in patients with performance status 0 or 1 experiencing hepatic IVC/VC, irrespective of liver function parameters and other factors.

Non-metastatic primary neuroendocrine neoplasms of the breast: a reference cancer center's experience of a heterogenous entity.

Background: Primary neuroendocrine neoplasms of the breast (Br-NENs) are rare. The classification has been updated in recent years making interpretation of the data published challenging. It is unclear whether neuroendocrine differentiation is associated with poorer prognosis and what treatment approaches should be applied. Methods: The database for breast cancer patients treated between 2009 and 2022 at the Maria Sklodowska-Curie National Research Institute of Oncology Branch Krakow was explored to search for Br-NENs. Patients' medical and pathological data were collected and analyzed. Results: We included 22 females with Br-NEN without metastases at the time of diagnosis. The median age was 64 years (range: 28-88), Of the cases, 18 were hormone receptor positive, all were HER-2 negative, the median Ki67 was 27% (10-100%). The median tumor size at the time of diagnosis was 29.5mm (7-75mm), 9 patients were N-positive. DCIS was present in 5 cases. Only one case was negative for chromogranin and synaptophysin staining, but data were missing for 4 cases. Nine patients received adjuvant chemotherapy, mainly based on anthracyclines and taxanes, while 16 received adjuvant hormonal therapy and 15 received postoperative radiotherapy. Radical surgery was performed in all patients, but two underwent suboptimal tumorectomy. One patient had local recurrence, three experienced metastatic disease, all involving the lungs, but these patients are still alive. The median follow-up was 96 months (8-153). Two patients died, with a follow up time of no recurrence >4 years. Our results were compared to twelve case series collecting clinical data on Br-NENs, with median patient number of 10.5 (range: 3-142). Conclusion: Br-NENs represent a heterogenous group of diseases, lacking data from prospective studies or clinical trials. There are no established treatment standards tailored for Br-NENs. Our patients' cohort exhibited a favorable prognosis, potentially attributed to lower tumor stage and Ki67 index compared to other reported case series. We suggest that radical surgery and postoperative radiotherapy be administered akin to standard treatment for breast cancer of no special type. ESMO also advocates for this approach in systemic treatment, although we recommend considering platinum-based chemotherapy for patients with poorly differentiated Br-NENs exhibiting high Ki67.

Clinical analysis of metaplastic breast carcinoma with distant metastases: A multi­centre experience.

Metaplastic breast cancer (BC-Mp), which includes a range of epithelial and mixed epithelial-mesenchymal tumours, are rare malignancies with an unfavourable prognosis. The limited literature on BC-Mp focuses mainly on retrospective data for radically treated patients. Notably absent are studies dedicated to the palliative treatment of BC-Mp with distant metastases. The present retrospective study investigated treatment modalities and prognosis in a multi-centre cohort of 31 female participants diagnosed with distant metastatic BC-Mp, including 7 patients with de novo metastatic disease. The median age of the patients was 61 years (range, 33-87 years), with 38.7% presenting local lymph node involvement. Lungs were the most common site for the metastatic disease (61.3%). Median Ki-67 index was 50% (range, 35-70%), and 80.7% of cases were classified as grade 3. Human epidermal growth factor receptor 2 (HER2)+ and estrogen receptor+ were detected in 12.9 and 6.5% of cases, respectively. A total of 62.4% of patients received first-line palliative systemic treatment. The 1- and 2-year overall survival (OS) were 38.5 and 19.2%, respectively. Receiving ≥1 line of palliative treatment was significantly associated with improved OS (P<0.001). Factors such as age, Ki-67 index, HER2 or hormonal status, presence of specific epithelial or mesenchymal components, location of metastases or chemotherapy regimen type did not influence OS. The present study provided insights into the clinicopathological profile, systemic treatment experience, prognostic factors and OS data of BC-Mp with distant metastases, emphasizing the imperative for clinical trials in this population.

Validation of the polish version of the eortc QLQ-C30 and the QLQ-OG25 for the assessment of health-related quality of life in patients with esophagi-gastric cancer.

The aim of this study was to validate the European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire Core 30 (QLQ-C30) and its esophagi-gastric module (QLQ-OG25) in their Polish language versions. Translation of the QLQ-OG25 was done according to EORTC guidelines. Each of the 98 patients filled out the two EORTC questionnaires and a personal questionnaire. Reliability and validity test were performed and patients' comments were analyzed. The Polish version of the EORTC QLQ-C30 and the QLQ-OG25 are reliable and valid tools for measuring health-related quality of life in patients with esophagi-gastric cancer.

The antineoplastic effect of low-molecular-weight heparins - a literature review.

There is some evidence for the antitumor effect of heparins, especially the low-molecular-weight ones. The authors discuss the potential mechanism of this antineoplastic effect and present results from several in vitro and in vivo experiments. The clinical trials concerning the impact of low-molecular-weight heparins on the tumor and on the patients' survival are described. The objective was to find out if heparins could be administered as an antitumor drug, independently of their anticoagulatory properties. The antitumor role of tissue factor, heparinase, chemokines, stromal proteins, cellular interactions as well as angiogenesis and immunology seems certain. The results of the available studies seem promising but large clinical trials are necessary in order to confirm the antineoplastic effect of the low-molecular-weight heparins and to approve them for standard anticancer treatment. It could be a breakthrough in modern oncology.