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Importance: Young women with breast cancer who have germline pathogenic variants in BRCA1 or BRCA2 face unique challenges regarding fertility. Previous studies demonstrating the feasibility and safety of pregnancy in breast cancer survivors included limited data regarding BRCA carriers., Objective: To investigate cumulative incidence of pregnancy and disease-free survival in young women who are BRCA carriers., Design, Setting, and Participants: International, multicenter, hospital-based, retrospective cohort study conducted at 78 participating centers worldwide. The study included female participants diagnosed with invasive breast cancer at age 40 years or younger between January 2000 and December 2020 carrying germline pathogenic variants in BRCA1 and/or BRCA2. Last delivery was October 7, 2022; last follow-up was February 20, 2023., Exposure: Pregnancy after breast cancer., Main Outcomes and Measures: Primary end points were cumulative incidence of pregnancy after breast cancer and disease-free survival. Secondary end points were breast cancer-specific survival, overall survival, pregnancy, and fetal and obstetric outcomes., Results: Of 4732 BRCA carriers included, 659 had at least 1 pregnancy after breast cancer and 4073 did not. Median age at diagnosis in the overall cohort was 35 years (IQR, 31-38 years). Cumulative incidence of pregnancy at 10 years was 22% (95% CI, 21%-24%), with a median time from breast cancer diagnosis to conception of 3.5 years (IQR, 2.2-5.3 years). Among the 659 patients who had a pregnancy, 45 (6.9%) and 63 (9.7%) had an induced abortion or a miscarriage, respectively. Of the 517 patients (79.7%) with a completed pregnancy, 406 (91.0%) delivered at term (≥37 weeks) and 54 (10.4%) had twins. Among the 470 infants born with known information on pregnancy complications, 4 (0.9%) had documented congenital anomalies. Median follow-up was 7.8 years (IQR, 4.5-12.6 years). No significant difference in disease-free survival was observed between patients with or without a pregnancy after breast cancer (adjusted hazard ratio, 0.99; 95% CI, 0.81-1.20). Patients who had a pregnancy had significantly better breast cancer-specific survival and overall survival., Conclusions and Relevance: In this global study, 1 in 5 young BRCA carriers conceived within 10 years after breast cancer diagnosis. Pregnancy following breast cancer in BRCA carriers was not associated with decreased disease-free survival., Trial Registration: ClinicalTrials.gov Identifier: NCT03673306.

Background: Pancreatic cancer remains one of the most challenging malignancies to treat, with consistently low survival rates despite advances in medical research. The identification and validation of effective prognostic biomarkers are crucial for improving diagnostic accuracy and treatment outcomes., Objective: The aim of the work is to analyze the latest data of the pancreatic cancer incidence and mortality, comparing them with global epidemiological data. The narrative review also aims to summarize current knowledge about various prognostic biomarkers in the pancreatic cancer treatment, including indicators of performance status, nutritional and inflammatory markers., Methods: The most recently available national epidemiological data on pancreatic cancer are analyzed. The literature review is focused on markers that evaluate the general condition of patients, such as performance status, body mass index, prognostic nutritional index and markers of the inflammatory response, such as Glasgow prognostic score, C-reactive protein, neutrophil to lymphocyte ratio, systemic inflammatory response index and systemic immune inflammation index. These biomarkers are analyzed for their role in predicting prognosis and response to systemic therapy for pancreatic cancer., Results: Both the Slovak Republic and the Czech Republic are globally ranked in the leading places in terms of pancreatic cancer incidence and mortality, both in estimates and real data. Indicators of nutritional and performance status play a critical role in patient assessment and influence treatment decisions, with potential impact on treatment outcomes. Inflammatory markers have shown significant prognostic value, correlating with the patient's immune response to the tumor and inflammatory processes that may promote disease progression. However, despite their promising predictive capabilities, these biomarkers are not routinely used in clinical practice due to the need for further validation., Conclusion: Integration of new biomarkers into clinical practice could lead to more personalized therapeutic decisions and improved treatment outcomes. Further research is needed for a more comprehensive assessment of the validity of these biomarkers and their use in common clinical conditions.

Alpelisib is an α-selective phosphatidylinositol 3-kinase inhibitor used for treating hormone receptor-positive (HR+), human epidermal growth receptor 2-negative (HER2-), PIK3CA -mutated locally advanced or metastatic breast cancer following disease progression on or after endocrine therapy. Hyperglycemia is an on-target effect of alpelisib affecting approximately 60% of treated patients, and sometimes necessitating dose reductions, treatment interruptions, or discontinuation of alpelisib. Early detection of hyperglycemia and timely intervention have a key role in achieving optimal glycemic control and maintaining alpelisib dose intensity to optimize the benefit of this drug. A glycemic support program implemented by an endocrinology-oncology collaborative team may be very useful in this regard. Lifestyle modifications, mainly comprising a reduced-carbohydrate diet, and a designated stepwise, personalized antihyperglycemic regimen, based on metformin, sodium-glucose co-transporter 2 inhibitors, and pioglitazone, are the main tools required to address the insulin-resistant hyperglycemia induced by alpelisib. In this report, based on the consensus of 14 oncologists and seven endocrinologists, we provide guidance for hyperglycemia management strategies before, during, and after alpelisib therapy for HR+, HER2-, PIK3CA -mutated breast cancer, with a focus on a proactive, multidisciplinary approach.

Following orchiectomy, patients with clinical stage I (CSI) testicular seminoma may be managed by active surveillance (S) or adjuvant treatment (radiotherapy or chemotherapy). In view of the published data on long-term toxicity, especially second malignant neoplasms (SMNs), adjuvant radiotherapy (ART) is currently no longer recommended as an adjuvant therapy option for these patients. The purpose of our recent study was to compare the impact of two selected treatment approaches - S versus adjuvant chemotherapy (ACT) on the survival of patients with CSI testicular seminoma. This cross-sectional study analyzed a total of 139 patients collected at a single center between 10/2011-5/2020, with CSI testicular seminoma, stratified into two groups according to risk-adapted therapeutic approaches. In the S group (low-risk - without rete testis invasion - RTI, primary tumor size <4 cm), consisting of 77 patients, who underwent S, relapse occurred in 10 (13.0%) patients after a mean follow-up of 14.3 months. In the ACT group (high-risk - RTI and/or primary tumor size >4 cm), consisting of 62 patients, who were treated with ACT, relapse occurred in 5 (8.1%) patients after a mean follow-up of 11.6 months. Overall survival of patients in both groups was 100% with a mean follow-up of 43.9 months. A statistically significant difference in progression-free survival (PFS) between these two groups was not found. Based on our findings, ACT seems to be an adequate treatment for patients with a high risk of relapse, as well as S for those with a low risk of relapse. Despite its excellent prognosis, optimal management of CSI testicular seminoma remains controversial, with variations in expert opinion and international guidelines.

Objective: This study analysed the characteristics and outcome of the patients with bilateral germ testicular cell cancer (TC), especially synchronous., Methods: Among 2.124 TC patients diagnosed between 1970 and 2020, 96 (4. 5%) developed the 2nd TC. Nine occurred synchronously and 87 were metachronous. Patients were analysed according to the age and histological type of bilateral TC in comparison with unilateral TC., Results: The mean follow-up of all 2,124 patients was 14.9 years. Unilateral TC occurred in 2.028 patients (the mean age of 32.4 years), 707 of them had seminoma, 1.310 nonseminomatous (NS) TC and 11 spermatocytic tumours. The 1st tumour of metachronous bilateral disease was diagnosed at a significantly younger age (27.1 years) compared to the unilateral disease (32.4 years). The mean interval between the 1st and the 2nd TC was 8.2 years. Patients with NSTC had a longer mean interval (9.2 years) between the 1st and the 2nd TC in comparison with seminoma patients (6.7 years). The mean age at diagnosis for seminoma was significantly higher (31.3 years) compared to the NSTC (24.1 years). Bilateral seminoma occurred in 5 synchronous bilateral TC patients, four patients had discordant histology, none presented with bilateral NSTC., Conclusions: Bilateral TC is a rare and requires individualized management of patients (Tab. 5, Fig. 4, Ref. 32).

The evidence that quality of life is a positive variable for the survival of cancer patients has prompted the interest of the health and pharmaceutical industry in considering that variable as a final clinical outcome. Sustained improvements in cancer care in recent years have resulted in increased numbers of people living with and beyond cancer, with increased attention being placed on improving quality of life for those individuals. Connected Health provides the foundations for the transformation of cancer care into a patient-centric model, focused on providing fully connected, personalized support and therapy for the unique needs of each patient. Connected Health creates an opportunity to overcome barriers to health care support among patients diagnosed with chronic conditions. This paper provides an overview of important areas for the foundations of the creation of a new Connected Health paradigm in cancer care. Here we discuss the capabilities of mobile and wearable technologies; we also discuss pervasive and persuasive strategies and device systems to provide multidisciplinary and inclusive approaches for cancer patients for mental well-being, physical activity promotion, and rehabilitation. Several examples already show that there is enthusiasm in strengthening the possibilities offered by Connected Health in persuasive and pervasive technology in cancer care. Developments harnessing the Internet of Things, personalization, patient-centered design, and artificial intelligence help to monitor and assess the health status of cancer patients. Furthermore, this paper analyses the data infrastructure ecosystem for Connected Health and its semantic interoperability with the Connected Health economy ecosystem and its associated barriers. Interoperability is essential when developing Connected Health solutions that integrate with health systems and electronic health records. Given the exponential business growth of the Connected Health economy, there is an urgent need to develop mHealth (mobile health) exponentially, making it both an attractive and challenging market. In conclusion, there is a need for user-centered and multidisciplinary standards of practice to the design, development, evaluation, and implementation of Connected Health interventions in cancer care to ensure their acceptability, practicality, feasibility, effectiveness, affordability, safety, and equity., (©Gabriel Ruiz Ruiz Signorelli, Fedor Lehocki, Matilde Mora Fernández, Gillian O'Neill, Dominic O'Connor, Louise Brennan, Francisco Monteiro-Guerra, Alejandro Rivero-Rodriguez, Santiago Hors-Fraile, Juan Munoz-Penas, Mercè Bonjorn Dalmau, Jorge Mota, Ricardo B Oliveira, Bela Mrinakova, Silvia Putekova, Naiara Muro, Francisco Zambrana, Juan M Garcia-Gomez. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 29.10.2019.)

Objectives: This study analyzes the incidence of multiple primary malignant neoplasms (MPN) in patients with testicular cancer (TC), the results are compared with literature findings and assess the rarest subgroup of patients with MPN., Patients and Methods: Clinical data of 1870 patients with TC treated or followed up in a single center in the period of 5/1970-12/2018 were collected and analyzed retrospectively in focus of the occurrence of MPN., Results: The overall incidence of MPN was 150 (8.02 %). There were 89 cases of bilateral TC (59.3 %), of these 8 cases were synchronous (diagnosed within three months period from the primary diagnosis) and 81 metachronous (9 % and 91 % respectively). Non-testicular other primary malignancies (OPM) occurred in 61 cases (40.7 %), of which 59 cases were metachronous (96.7 %) and two cases were synchronous (3.3 %). Metachronous malignancies included mainly prostate cancer (n = 17 patients), kidney cancer (n = 13 patients) and colorectal cancer (n = 12 patients). Synchronous OPM was found in two patients., Conclusion: In our study we registered two cases of synchronous OPM, both histologically clear cell renal cancer. We have analyzed clinical characteristics, diagnosis and treatment strategies of synchronous OPM, in order to improve its diagnosis and therapy (Fig. 3, Ref. 22).

Background: Penile cancer belongs to group of relatively rare malignancies. It represents, on average, 0.5-1% of all tumours in males globally and occurs predominantly in older individuals (&gt; 65 years). The geographical distribution of malignant cancer of the penis is reported. A higher incidence is observed in less developed parts of the world, particularly in South America, Southeast Asia, and some areas of Africa (&gt; 2.0/100,000). In Slovakia, there has been a recent increase in incidence (1.1/100,000 in 2011). Mortality has stabilized at 0.3/100,000 in recent years. Significant risk factors for malignant cancers include social and cultural habits and hygienic and religious practices. Important risk factors are inadequate hygiene of the foreskin sac, phimosis, human papillomavirus infection, sexual promiscuity, smoking, genital infections, and a low socio-economic and educational status., Purpose: The present paper provides an overview of pathology, symptomatology, diagnostic approaches, and classification of the extent of the disease. Treatment of the primary tumour depends on the extent of the disease and includes topical treatment, photodynamic treatment, cryoablation, laser photocoagulation, conservative surgical treatment, especially circumcision, and even radical treatment - penile amputation with perineal urethrostomy. An important part of the management of this malignancy is surgical treatment of metastases in inguinal lymph nodes. The article devotes more attention to non-surgical treatment modalities, in particular radiotherapy (external and brachytherapy) and systemic therapy (chemotherapy and biologic therapy), offering an overview of the indications and regimens in the adjuvant, neoadjuvant and palliative approaches, with and without concomitant chemoradiotherapy, and describes possible adverse effects of the treatments.  Conclusion: Patients with penile cancer should be concentrated in centres that have abundant experience in the diagnosis and treatment of this disease. Key words penile cancer - surgical treatment - radiotherapy - chemotherapy - biologic therapy The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. Submitted: 12. 11. 2018 Accepted: 12. 12. 2018.

Paratesticular malignant mesothelioma is an extremely rare type of mesothelioma with only a limited number of reported cases. Its clinical differentiation is challenging, and its diagnosis is almost exclusively accidental. The major risk factor is exposure to asbestos, typically with a long latency between exposure and diagnosis. The current study presents the clinical data of two patients diagnosed with paratesticular malignant mesothelioma. We evaluated a large spectrum of risk factors in the patients histories. The histomorphological and immunohistochemical characteristics were analysed and put into the perspective of a broad differential diagnosis. Both cases of malignant epithelial mesothelioma of the tunica vaginalis testis clinically presented as unilateral hydroceles. Patients underwent surgery with the perioperative finding of a tumour. Radical inguinal orchiectomy was the treatment of choice for both patients. After comprehensive staging, the second patient underwent a second step of inguinal and pelvic lymph node dis- section. Follow-up visits revealed recurrence of the disease in the first patient. Resection of the tumour was performed. The histology confirmed the relapse of a tumour with identical features to those of the first tumour. Chemotherapy and radiotherapy were not indicated. Both patients are currently in complete remission. In conclusion, surgical treatment had a determinative role in the prognosis of these patients. Radical orchiectomy is the treatment of choice for localized disease. Lymph node dissection can be considered in the case of lymph node enlargement. There is a lack of evidence-based data for adjuvant chemotherapy and radiotherapy. Patients should be referred to experienced multidisciplinary cancer centres for a second opinion on histology, treatment, and a follow-up plan.Key words: mesothelioma - tunica vaginalis testis - hydrocele - asbestos exposure.

Introduction: Following orchiectomy patients with clinical stage I (CSI) testicular seminoma may be managed by active surveillance (AS) or adjuvant treatment (radiotherapy or chemotherapy). In view of the published data on long-term toxicity, mainly second malignant neoplasms (SMNs), adjuvant radiotherapy (ART) is currently no longer recommended as adjuvant therapy for these patients. The purpose of our recent study was to compare the impact of two selected treatment approaches - AS versus adjuvant chemotherapy (ACT) on survival in patients with CSI testicular seminoma., Material and Methods: The cross-sectional study analyzed a total of 106 patients collected at a single centre between 4/2008-8/2015, with CSI testicular seminoma, stratified into two groups according to risk-adapted therapeutic approaches., Results: In group A (low-risk), consisting of 84 patients, who underwent AS, relapse occurred in 10 (11.9%) patients after a mean follow-up of 13.8 months. In group B (high-risk), consisting of 22 patients, who were treated with ACT, relapse occurred in two (9.1%) patients after a mean follow-up of 13.8 months. Overall survival of patients in both groups was 100% with a mean follow-up of 25.3 months. The statistically significant difference in progression-free survival (PFS) between these two groups was not found., Conclusions: ACT seems to be adequate treatment for patients with high-risk of relapse, as well as AS for those with low-risk of relapse. Despite its excellent prognosis, optimal management of CSI testicular seminoma remains controversial, with variations in expert opinion and international guidelines.

Background: Primary intracranial germ cell tumors represent a rare category of neoplasms, which occur in children and young adults. The WHO classification divides intracranial tumors into germinomas and non-germinomas. The most frequent locality of these tumors is pineal and suprasellar region. Clinical signs and symptoms depend on the localization of the tumour - they most commonly include signs of increased intracranial pressure, Parinauds syndrome, bitemporal hemianopsy and signs of endocrine deficiency. Gadolinium enhanced MRI scan of the brain is the imagining examination of choice in the diagnostic strategy of intracranial germ cell tumors. However, the imagining studies do not provide sufficient information about histological type; therefore, biopsy is necessary. The exception represents cases with characteristically increased levels of tumor markers (AFP and β-HCG) measured in the serum and cere-brospinal fluid., Case: A pineal germ cell tumor was observed in a 26-year-old male with presentation of an eye-sight disorder with focusing difficulty and photophobia, accompanied by intensive fatigue and sleepiness, nausea with occasional vomiting, intermittent headaches and Parinauds syndrome. MRI examination of the brain showed tumor expansion in the pineal region and in the right part of the mesencephalon. Radical extirpation of the tumor in the pineal region was performed. The follow-up MRI scan of the brain revealed relapse of the disease. The patient underwent craniospinal radiation therapy with subsequent postoperative chemotherapy (regimen cisplatin and etoposide), three cycles in total. Currently, the patient is 30 months after finishing of oncological treatment in clinical remission of the disease., Conclusion: The treatment and prognosis of this neoplasm differ between particular categories. Germinomas have better survival rates than non-germinomas. A 5-year survival rate of germinoma patients after application of radiotherapy alone was > 90% of cases. The addition of chemotherapy lead to a decrease of the dose and minimalization of the irradiated area, with achievement of fewer side effects without a decrease of the curability. Non-germinomas are less radiosensitive than germinomas, but after the application of the adjuvant chemotherapy, survival benefit was achieved. However, the optimal management of these tumors remains controversial.

An increase in melanoma incidence in the Slovak Republic (SR) is evident during approximately the same time and maybe caused by changes in socio-economic status. The paper analyses national trends in incidence, mortality, survival and clinical stages of invasive cutaneous melanoma in the SR from 1968-2007. The trends in incidence and mortality have been extracted between 1968-2007 period by the joinpoint regression analysis, clinical stages were analysed in 1978-2003. Survival data were extracted from the national database resources. Socio-economic changes, which reflected in increase in the number of holiday makers to seaside and mountainous destinations happened in the country in the y.1989. Subsequently, according to joinpoint in 1997, acceleration of increment of the incidence values of melanoma was recorded in both sexes. Mortality was increasing in males continuously, in females the stabilization was registered after the year 1999. Lower rates of relative survival might be influenced by delayed accessibility to adjuvant treatment. The number of cases diagnosed in clinical stage I increased significantly. The changes in the intensity and excessive sunbathing during vacations might be one of many factors that participate in subsequent acceleration of the increment of incidence not only in the SR.

Background: Malignant mesothelioma is a neoplasm arising in serosal membranes in the body cavities. Usual presentation of the tumor is in the pleura, peritoneum and less frequently pericardium. Paratesticular mesothelioma is the rarest known form of malignant mesothelioma with only a limited number of reported cases., Case: A case of malignant epithelial mesothelioma of the tunica vaginalis testis was reported with presentation of hydrocele and multinodular intrascrotal masses in a 20-year old male. The patient underwent surgery for post-traumatic long-term hydrocele with perioperative discovery of multiple small exophytic structures. After histological findings of the malignant mesothelioma of tunica vaginalis testis, he underwent left-side orchiectomy, followed by inguinal and pelvic lymph node dissection. Clinical staging did not reveal distant metastases. Regular follow-up visits based on physical examinations and imaging studies are to date negative for recurrence., Conclusion: Literature data were reviewed, and possible risk factors for the development of the neoplasm were analysed.