BACKGROUND: The possibilities of adjuvant therapy of malignant melanoma have significantly expanded in recent years. Based on the results of clinical studies, immunotherapy represented by checkpoint inhibitors (ipilimumab, pembrolizumab, nivolumab) and targeted therapies (dabrafenib plus trametinib) in patients with a proven mutation in the BRAF gene were included in the treatment protocols. In the Czech Republic, nivolumab and combination therapy of dabrafenib with trametinib are currently available for clinical practice. However, the question remains how to proceed if relapse or generalization occurs after the adjuvant treatment. The following case study describes one of possible solutions. CASE REPORT: The article presents the failure of adjuvant nivolumab immunotherapy in a patient with locally advanced stage IIIC malignant melanoma. Ipilimumab has been selected as a treatment choice and demonstrated its efficacy. However, its administration was associated with immune-related side effects. These were dia-gnosed and successfully treated in the internal department in close cooperation with our department of oncology. CONCLUSION: Although adjuvant therapy has significantly reduced a risk of disease relapse, there is a cohort of patients in whom adjuvant therapy fails. Failure may occur after the end of the therapy or, as in our case, during the therapy. Based on currently available data, it is not possible to unambiguously choose the optimal procedure after adjuvant therapy failure. Currently, there is no other way than following clinical experience and reimbursement regulations, or enrolling the patient in a clinical trial. Immune-related adverse effects require particular attention as they are unique due to their mechanism of origin and often require a multidisciplinary approach.

• Klíčová slova
• adjuvant therapy, ipilimumab, malignant melanoma, melanoma, nivolumab,
• MeSH
• adjuvantní chemoterapie * MeSH
• imunoterapie MeSH
• inhibitory kontrolních bodů terapeutické užití   MeSH
• lidé MeSH
• melanom farmakoterapie   MeSH
• neúspěšná terapie MeSH
• nivolumab terapeutické užití   MeSH
• protinádorové látky imunologicky aktivní terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Názvy látek
• inhibitory kontrolních bodů MeSH
• nivolumab MeSH
• protinádorové látky imunologicky aktivní MeSH

The objective of this study was to compare the actual outcome and prognosis estimated by the program Adjuvant! Online for breast cancer in Itajaí (Brazil). It is a retrospective cohort study, post-hoc analysis, in which 214 patients of three institutions were compared in real overall survival (OS) and disease-free survival (DFS) during a 3-year follow-up, and estimated OS and DFS with the program for 10 years by Adjuvant! Online, using the following variables: age, clinical stage, histological grade, lymph node involvement, immunohistochemical subtype and type of adjuvant therapy. The DFS and OS rates in the sample observed and estimated by the program demonstrated correspondence, with the curves trailing beneath the same pattern, due to shorter "real" follow-up (3 versus 10 years). The only group that demonstrated a marked decline in DFS in relation to the real prognosis was that of patients younger than 40 years.

• MeSH
• adjuvantní chemoterapie * MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• míra přežití MeSH
• nádory prsu farmakoterapie   mortalita   MeSH
• přežití bez známek nemoci MeSH
• prognóza MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

OBJECTIVE: To evaluate the impact of adjuvant therapy on oncological outcomes in patients with intermediate-risk non-muscle-invasive bladder cancer (NMIBC), as due to the poorly-defined and overlapping diagnostic criteria optimal decision-making remains challenging in these patients. PATIENTS AND METHODS: In this multicentre study, patients treated with transurethral resection of bladder tumour for Ta disease were retrospectively analysed. All patients with low- or high-risk NMIBC were excluded from the analysis. Associations between adjuvant therapy administration with recurrence-free survival (RFS) and progression-free survival (PFS) rates were assessed in Cox regression models. RESULTS: A total of 2206 patients with intermediate-risk NMIBC were included in the analysis. Among them, 1427 patients underwent adjuvant therapy, such as bacille Calmette-Guérin (n = 168), or chemotherapeutic agents, such as mitomycin C or epirubicin (n = 1259), in different regimens up to 1 year. The median (interquartile range) follow-up was 73.3 (38.4-106.9) months. The RFS at 1 and 5 years in patients treated with adjuvant therapy and those without were 72.6% vs 69.5% and 50.8% vs 41.3%, respectively. Adjuvant therapy was associated with better RFS (hazard ratio [HR] 0.79, 95% confidence interval [CI] 0.70-0.89, P < 0.001), but not with PFS (P = 0.09). In the subgroup of patients aged ≤70 years with primary, single Ta Grade 2 <3 cm tumours (n = 328), adjuvant therapy was not associated with RFS (HR 0.71, 95% CI 0.50-1.02, P = 0.06). While in the subgroup of patients with at least one risk factor including patient age >70 years, tumour multiplicity, recurrent tumour and tumour size ≥3 cm (n = 1878), adjuvant intravesical therapy was associated with improved RFS (HR 0.78, 95% CI 0.68-0.88, P < 0.001). CONCLUSION: In our study, patients with intermediate-risk NMIBC benefit from adjuvant intravesical therapy in terms of RFS. However, in patients without risk factors, adjuvant intravesical therapy did not result in a clear reduction in the recurrence rate.

• Klíčová slova
• BCG, NMIBC, adjuvant, chemotherapy, intravesical,
• MeSH
• adjuvantní chemoterapie MeSH
• aplikace intravezikální MeSH
• BCG vakcína terapeutické užití   aplikace a dávkování   MeSH
• cystektomie metody   MeSH
• epirubicin aplikace a dávkování   MeSH
• invazivní růst nádoru MeSH
• lidé středního věku MeSH
• lidé MeSH
• mitomycin aplikace a dávkování   terapeutické užití   MeSH
• nádory močového měchýře neinvadující svalovinu MeSH
• nádory močového měchýře * patologie   terapie   farmakoterapie   mortalita   MeSH
• přežití bez známek nemoci MeSH
• retrospektivní studie MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• Názvy látek
• BCG vakcína MeSH
• epirubicin MeSH
• mitomycin MeSH

Melatonin is a hormone with strong antioxidant properties. In this experiment, Freund's complete adjuvant was used as a stressogenic substance given to laboratory outbred mice, whereas melatonin was investigated as a protectant against the stressogenic effect. Levels of low molecular weight antioxidants, thiobarbituric acid reactive substances, and tumor necrosis factor α and activity of glutathione reductase were determined in blood from the animals. Surprisingly, melatonin was not involved in direct regulation of antioxidants, thiobarbituric acid reactive substances and tumor necrosis factor α. On the other hand, melatonin regulated glutathione reductase activity. We can conclude on regulation of metabolism caused by melatonin in the model. The effect was more important than the expected regulation of immunity and basal oxidative homeostasis.

• Klíčová slova
• Antioxidant, Epiphysis, Hormone, Melatonin, Oxidative stress, Reactive oxygen species,
• MeSH
• adjuvancia imunologická farmakologie   MeSH
• antioxidancia farmakologie   fyziologie   MeSH
• Freundovo adjuvans farmakologie   MeSH
• melatonin farmakologie   fyziologie   MeSH
• myši MeSH
• oxidační stres účinky léků   fyziologie   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• adjuvancia imunologická MeSH
• antioxidancia MeSH
• Freundovo adjuvans MeSH
• melatonin MeSH

New chemical agents encountered increasingly in the human environment underline the urgent need for a routine testing of their sensitizing potential for man and the development of a suitable experimental model appears to be essential for a reliable assessment of this potential. In our present experiment we studied a guinea pig model of contact hypersensitivity to chromium using as immunoadjuvants Freund's complete adjuvant (FCA) and Freund's incomplete adjuvant (FIA) emulsified with muramyldipeptide. The study showed that the use of adjuvants was essential for inducing the state of hypersensitivity in experimental animals. It was also demonstrated that muramyldipeptide was not only a fully potent substitute for FCA, but was even superior to it in all the parameters tested. The optimal time interval for demonstrating the induced hypersensitivity to chromium was the third week after the onset of sensitization. This animal model appears to be well suited for the experimental testing of contact allergen potentials.

• MeSH
• acetylmuramyl-alanyl-isoglutamin * imunologie   MeSH
• adjuvancia imunologická * MeSH
• chrom škodlivé účinky   MeSH
• Freundovo adjuvans MeSH
• kontaktní dermatitida etiologie   MeSH
• morčata MeSH
• zvířata MeSH
• Check Tag
• morčata MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• acetylmuramyl-alanyl-isoglutamin * MeSH
• adjuvancia imunologická * MeSH
• chrom MeSH
• Freundovo adjuvans MeSH

The activation of tumor-specific effector immune cells is key for successful immunotherapy and vaccination is a powerful strategy to induce such adaptive immune responses. However, the generation of effective anticancer vaccines is challenging. To overcome these challenges, a novel straight-forward strategy of adjuvant-induced tumor antigen assembly to generate nanovaccines with superior antigen/adjuvant loading efficiency is developed. To protect nanovaccines in circulation and to introduce additional functionalities, a biocompatible polyphenol coating is installed. The resulting functionalizable nanovaccines are equipped with a pH (low) insertion peptide (pHLIP) to facilitate endolysosomal escape and to promote cytoplasmic localization, with the aim to enhance cross-presentation of the antigen by dendritic cells to effectively activate CD8+ T cell. The results demonstrate that pHLIP-functionalized model nanovaccine can induce endolysosomal escape and enhance CD8+ T cell activation both in vitro and in vivo. Furthermore, based on the adjuvant-induced antigen assembly, nanovaccines of the clinically relevant tumor-associated antigen NY-ESO-1 are generated and show excellent capacity to elicit NY-ESO-1-specific CD8+ T cell activation, demonstrating a high potential of this functionalizable nanovaccine formulation strategy for clinical applications.

• Klíčová slova
• T cell activation, antigen/adjuvant codelivery, cancer nanovaccines, cross-presentation, endolysosomal escape,
• MeSH
• adjuvancia imunologická MeSH
• aktivace lymfocytů fyziologie   MeSH
• antigeny nádorové imunologie   MeSH
• buněčné linie MeSH
• CD8-pozitivní T-lymfocyty metabolismus   MeSH
• kinetika MeSH
• lidé MeSH
• polyfenoly chemie   MeSH
• protinádorové vakcíny imunologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• adjuvancia imunologická MeSH
• antigeny nádorové MeSH
• polyfenoly MeSH
• protinádorové vakcíny MeSH

BACKGROUND: The adjuvant radiotherapy (RT) of the early-stage breast cancer patients as local treatment aims to eliminate potential microscopic residual disease in the surgery bed or satellites in its neighborhood. Based on published studies, accelerated partial breast irradiation (APBI) is recommended for strictly selected patients. The aim of this single-institution prospective randomized study was to compare the targeted APBI delivered by stereotactic approach with the currently more commonly used accelerated whole breast irradiation with the boost to the tumor bed in terms of feasibility, safety, tolerance, and cosmetic effects. MATERIALS AND METHODS: Early-stage breast cancer patients after partial mastectomy were screened for eligibility. The inclusion criteria were age > 50 years, non-lobular carcinoma histology, size 2cm, negative margins 2mm, L0, ER-positive, BRCA negative. Enrolled patients were equally randomized into two arms according to radiotherapeutic regiment - external APBI (5× 6 Gy) and accelerated whole breast irradiation with the boost (15× 2,67 Gy + 5× 2 Gy). These preliminary results of the ongoing study evaluated the first 57 from 84 planned patients. RESULTS: The median age was 65 years. The tumors were of grade 1 in 60 % of patients, the median size of 9mm and 70 % were classified as invasive ductal carcinoma. Statistical significant differences between the groups in baseline characteristics were not observed. A total of 29 patients was enrolled in the APBI group by the end of 2020. All enrolled patients were evaluated one month after RT. A total of 40 (70,2 %) a 33 (58 %) had examinations 3 and 6 months after RT, respectively. Toxicity evaluation showed statistically significantly fewer acute adverse events in the APBI group in terms of skin erythema, desquamation, skin tenderness, dryness, edema, pigmentation, breast pain and fatigue. Late toxicity evaluated in 3 and 6 months after RT was significantly higher in the control group. The cosmetic effect (independently evaluated by a physician, nurse and patient) was more favorable to the APBI group. CONCLUSION: The technique using the principles of targeted radiotherapy turned out to be a less toxic and easier feasible approach for adjuvant radiation of early-stage breast cancer patients. Consequently, the presented study increases the level of evidence for RT-indicated patients to the establishment of external APBI into daily clinical practice.

• Klíčová slova
• APBI, adjuvant radiotherapy, breast cancer, early stages, radiotherapy adjuvant, stereotactic body radiotherapy, surgical bed,
• MeSH
• adjuvancia imunologická MeSH
• adjuvantní radioterapie MeSH
• lidé středního věku MeSH
• lidé MeSH
• mastektomie MeSH
• nádory prsu * radioterapie   chirurgie   MeSH
• prospektivní studie MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• adjuvancia imunologická MeSH

OBJECTIVE: The "intermediate-risk" (IR) group of early-stage cervical cancer patients is characterized by negative pelvic lymph nodes and a combination of tumor-related prognostic risk factors such as tumor size ≥2 cm, lymphovascular space invasion (LVSI), and deep stromal invasion. However, the role of adjuvant treatment in these patients remains controversial. We investigated whether adjuvant (chemo)radiation is associated with a survival benefit after radical surgery in patients with IR cervical cancer. METHODS: We analyzed data from patients with IR cervical cancer (tumor size 2-4 cm plus LVSI OR tumor size >4 cm; N0; no parametrial invasion; clear surgical margins) who underwent primary curative-intent surgery between 2007 and 2016 and were retrospectively registered in the international multicenter Surveillance in Cervical CANcer (SCCAN) study. RESULTS: Of 692 analyzed patients, 274 (39.6%) received no adjuvant treatment (AT-) and 418 (60.4%) received radiotherapy or chemoradiotherapy (AT+). The 5-year disease-free survival (83.2% and 80.3%; PDFS = 0.365) and overall survival (88.7% and 89.0%; POS = 0.281) were not significantly different between the AT- and AT+ groups, respectively. Adjuvant (chemo)radiotherapy was not associated with a survival benefit after adjusting for confounding factors by case-control propensity score matching or in subgroup analyses of patients with tumor size ≥4 cm and <4 cm. In univariable analysis, adjuvant (chemo)radiotherapy was not identified as a prognostic factor in any of the subgroups (full cohort: PDFS = 0.365; POS = 0.282). CONCLUSION: Among patients with IR early-stage cervical cancer, radical surgery alone achieved equal disease-free and overall survival rates to those achieved by combining radical surgery with adjuvant (chemo)radiotherapy.

• Klíčová slova
• Adjuvant treatment, Cervical cancer, GOG criteria, Intermediate risk, Radial surgery, Radiotherapy,
• MeSH
• adjuvantní radioterapie MeSH
• hysterektomie MeSH
• kombinovaná terapie MeSH
• lidé MeSH
• nádory děložního čípku * patologie   MeSH
• prognóza MeSH
• retrospektivní studie MeSH
• staging nádorů MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH

Cardiac surgery patients are now more risky in terms of age, comorbidities, and the need for complex procedures. It brings about reperfusion injury, which leads to dysfunction and/or loss of part of the myocardium. These groups of patients have a higher incidence of postoperative complications and mortality. One way of augmenting intraoperative myocardial protection is the phenomenon of myocardial conditioning, elicited with brief nonlethal episodes of ischaemia-reperfusion. In addition, drugs are being tested that mimic ischaemic conditioning. Such cardioprotective techniques are mainly focused on reperfusion injury, a complex response of the organism to the restoration of coronary blood flow in ischaemic tissue, which can lead to cell death. Extensive research over the last three decades has revealed the basic mechanisms of reperfusion injury and myocardial conditioning, suggesting its therapeutic potential. But despite the enormous efforts that have been expended in preclinical studies, almost all cardioprotective therapies have failed in the third phase of clinical trials. One reason is that evolutionary young cellular mechanisms of protection against oxygen handling are not very robust. Ischaemic conditioning, which is among these, is also limited by this. At present, the prevailing belief is that such options of treatment exist, but their full employment will not occur until subquestions and methodological issues with the transfer into clinical practice have been resolved.

• MeSH
• adjuvancia farmaceutická terapeutické užití   MeSH
• ischemický postconditioning MeSH
• kardiochirurgické výkony * škodlivé účinky   MeSH
• kardiotonika terapeutické užití   MeSH
• klinické zkoušky jako téma MeSH
• lidé MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• adjuvancia farmaceutická MeSH
• kardiotonika MeSH

The role of postmastectomy radiotherapy and regional nodal irradiation after radical mastectomy is defined in high-risk patients with locally advanced tumors, positive margins, and unfavorable biology. The benefit of postmastectomy radiotherapy in intermediate-risk patients (T3N0 tumors) remains a matter of controversy. It has been demonstrated that radiotherapy after breast-conserving surgery lowers the locoregional recurrence rate compared with surgery alone and improves the overall survival rate. In patients with four or more positive lymph nodes or extracapsular extension, regional lymph node irradiation is indicated regardless of the surgery type (breast-conserving surgery or mastectomy). Despite the consensus that patients with more than three positive lymph nodes should be treated with radiotherapy, there is controversy regarding the recommendations for patients with one to three involved lymph nodes. In patients with N0 disease with negative findings on axillary surgery, there is a trend to administer regional lymph node irradiation in patients with a high risk of recurrence. In patients treated with neoadjuvant systemic therapy and mastectomy, adjuvant radiotherapy should be administered in cases of clinical stage III and/or ≥ypN1. In patients treated with neoadjuvant systemic therapy and breast-conserving surgery, postoperative radiotherapy is indicated irrespective of pathological response.

• Klíčová slova
• adjuvant radiotherapy, breast cancer, breast-conserving surgery, mastectomy, neoadjuvant chemotherapy, regional node irradiation, whole breast irradiation,
• MeSH
• adjuvantní radioterapie MeSH
• lidé MeSH
• lokální recidiva nádoru patologie   MeSH
• mastektomie MeSH
• nádory prsu * farmakoterapie   MeSH
• segmentální mastektomie MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH