Current Treatment of Melanoma Brain Metastases.

Melanoma is a type of skin cancer in which there is a strong correlation between its occurrence and exposure to ultraviolet radiation. Although it is not the most common skin cancer, it has the highest mortality rate of all skin cancers. The prognosis of patients is significantly worsened by melanoma metastasis to the brain, which often occurs in patients with advanced disease. The formation and development of melanoma metastases to the brain involve a very complex process, and their mechanisms are not fully understood. One of the ways for metastatic melanoma cells to survive and develop cancer in the brain environment is the presence of oncogenic BRAF mutation, which occurs in up to 50% of metastatic melanoma cases. Before discovering new methods of treating metastases, the overall survival of patients with this disease was 6 months. Currently, research is being conducted on new drugs using immunotherapy (immune checkpoint inhibitors: anti-PD-1, anti-CTLA-4) and targeted therapy (BRAF and MEK inhibitors) to improve the prognosis of patients. In this article, we summarize the current state of knowledge about the results of treating brain metastases with new systemic therapies.

Dietary Fish Meal Replacement with Hermetia illucens and Tenebrio molitor Larval Meals Improves the Growth Performance and Nutriphysiological Status of Ide (Leuciscus idus) Juveniles.

The ide (Leuciscus idus) is a native European species of rheophilic cyprinid fish whose wild population status is dependent on conservation efforts, particularly regular restocking. This study aimed to evaluate the effects of including insect meals as a component in the diet of ide juveniles on their growth performance, feed utilization, and nutriphysiological status. Four diets were formulated: three with insect meals, HI-with 20% Hermetia illucens meal, TM-with 20% Tenebrio molitor meal, and ZM-with 20% Zophobas morio meal, and the control group diet, CON-fish meal with no insect component. The effects of the various diets on the efficiency of rearing ide juveniles were assessed based on fish growth parameters, feed utilization parameters, somatic indices, and intestinal and hepatopancreatic histomorphology. The highest increase in fish weight gain and the protein efficiency ratio was observed in the HI and TM groups, while the lowest values were observed in the CON and ZM groups. Comparable results were noted for the feed conversion ratio, which was most favorable in the HI and TM groups and increased in the ZM group. The use of black soldier fly and mealworm larval meal in the diets of ide juveniles had a positive effect on rearing results and overall fish health.

Pain Management Strategies among Cancer Patients. Normalization of the CSQ (The Pain Coping Strategies Questionnaire) Form.

INTRODUCTION: Cancer is associated with chronic pain, which significantly reduces the quality of life. The level of pain depends on the dominant pain management strategy that the patient uses. OBJECTIVE: This study seeks to evaluate the application of the Pain Coping Strategies Questionnaire among cancer patients and develop norms allowing differentiation of patients with diagnosed cancer in terms of pain management strategies. MATERIAL AND METHODS: The study involved 1187 patients diagnosed with malignant cancer, who are under outpatient care of the Maria Sklodowska-Curie Institute-Oncology Center in Warsaw. The study used the Pain Coping Strategies Questionnaire (CSQ) elaborated by A.K. Rosentel and F.J. Keefe. RESULTS: Socioeconomic variables and medical factors affect pain management strategies chosen by patients. The area most strongly differentiated by the studied variables is praying/hoping. Factors that have the greatest impact on the choice of pain management strategies for cancer patients include education, income, and radiation therapy. Sten standards were developed to determine the severity of pain management strategies used in the low-average-high categories. CONCLUSIONS: The CSQ questionnaire should be used in cancer patients, and the result of the strategy used can be a prognostic factor for the expected effects of therapy. Knowledge of the variables most strongly affecting patients' choice of strategies that are not conducive to strengthening health attitudes and the ability to determine the severity of pain management strategies on standard scales allows us to focus psychotherapeutic activities on patients who need support most.

Modulation of Intestinal Histology by Probiotics, Prebiotics and Synbiotics Delivered In Ovo in Distinct Chicken Genotypes.

The aim of the study was to determine the effect of probiotics, prebiotics and synbiotics administered in ovo on selected morphological parameters of the small intestine (duodenum, jejunum, ileum) in broiler chickens (Ross 308) and native chickens (Green-legged Partridge, GP). On the 12th day of embryonic development (the incubation period), an aqueous solution of a suitable bioactive substance was supplied in ovo to the egg's air cell: probiotic-Lactococcus lactis subsp. cremoris (PRO), prebiotic-GOS, galacto-oligosaccharides (PRE) or symbiotic-GOS + Lactococcus lactis subsp. cremoris (SYN). Sterile saline was injected into control (CON) eggs. After hatching, the chicks were placed in pens (8 birds/pen, 4 replicates/group) and housed for 42 days. On the last day of the experiment, all birds were individually weighed and slaughtered. Samples for histological analysis were taken directly after slaughter from three sections of the small intestine. In samples from the duodenum, jejunum and ileum, the height and width of the intestinal villi (VH) were measured and their area (VA) was calculated, the depth of the intestinal crypts (CD) was determined, the thickness of the muscularis was measured and the ratio of the villus height to the crypt depth (V/C) was calculated. On the basis of the obtained data, it can be concluded that the applied substances administered in ovo affect the production parameters and intestinal morphology in broiler chickens and GP. The experiment showed a beneficial effect of in ovo stimulation with a prebiotic on the final body weight of Ross 308 compared to CON, while the effect of the administered substances on the intestinal microstructure is not unequivocal. In GP, the best effect in terms of villi height and V/C ratio was found in the in ovo synbiotic group. Taking into account the obtained results, it can be concluded that chickens of different genotypes react differently to a given substance; therefore, the substances should be adapted to the genotype.

Effects of a Trans-Galactooligosaccharide on Minerals Content of Common Carp (Cyprinus carpio L.) Tissues.

Common carp (Cyprinus carpio L.) is a dominant fish species in aquaculture, and as it is a stomachless species, absorption and digestion of nutrients take place in the intestine. The aim of the study was to evaluate the effects of a prebiotic on the content of selected minerals found in the meat, gills, and skeleton of common carp. The research applied trans-galactooligosaccharide (GOS) prebiotic produced by enzymatic transgalactosylation of milk lactose by whole cells of Bifidobacterium bifidum. The following diets have been applied: control diet without feed additives (C), diet 2 (B1) with 1% of GOS, and diet 3 (B2) with 2% of GOS. In the freeze-dried samples, concentrations of the analyzed metals were determined using atomic absorption spectroscopy (AAS). The content of phosphorus was determined using colorimetric method. The analyses confirmed that the highest level of Mg was detected in the skeleton of fish fed with 1% GOS (2.51 g kg-1) and was significantly higher compared the control treatment (2.11 g kg-1) (P < 0.05). Zn content in fish meat fed with 1% GOS (35.41 mg kg-1) was significantly higher (P < 0.05) than in the control group (24.59 mg kg-1). The tissue that accumulated the greatest amount of Zn was the gills. GOS had a positive effect on Fe accumulation in the meat, gills, and skeleton. It has been concluded that supplementation of feed with 2% GOS significantly influenced the positive correlations between Mg and P in the meat and skeleton, Fe-Ca correlation in gills, and Fe-Zn correlation in the skeleton.

Effects of a Trans-Galactooligosaccharide on Biochemical Blood Parameters and Intestine Morphometric Parameters of Common Carp (Cyprinus carpio L.).

: The aim of the study was to evaluate the effects of a trans-galactooligosaccharide prebiotic (GOS) on the growth performance, biochemical blood parameters, and intestine morphometric parameters of common carp. The 60-day-long experiment was performed on one-year-old fish with a mean body weight of 180 g (±5 g). Three diets were used: control diet 1 (C) with no microbiota affecting feed additives, diet 2 (B1) with 1% of prebiotic, and diet 3 (B2) with 2% of prebiotic, in four replications (tanks) per treatment and 25 fish per tank. At the end of the trial, 16 individuals from each group were used for analyses. The study showed that GOS supplementation did not affect growth performance. In turn, the prebiotic had a positive effect on the development of the intestine, and increased the height, width, and surface of the villi in B1 and B2 groups. The content of phosphorus (P) was significantly higher in B1 group compared with B2 group, which indicated that 1% addition of prebiotic causes better absorption of P from the intestine. The other biochemical indicators-namely lipid, protein and hepatic parameters, insulin, and Ca-were not affected by GOS treatment, which may indicate similar metabolic balance of fish in each experimental group. Serum triiodothyronine (TT3) and glucose (stress markers) concentrations were not significantly different among treatments groups. GOS may be recommended as a feed additive for common carp due to its positive effects on fish physiology and development of the gastrointestinal tract. However, our results suggest that 1% diet supplementation causes satisfactory reactions for the abovementioned aspects in comparison to control or 2% supplementation.

The role of postoperative radiotherapy in prostate cancer patients.

AIM OF THE STUDY: The aim of the study was to evaluate the effectiveness of postoperative radiotherapy in prostate cancer patients with unfavorable prognostic factors. MATERIAL AND METHODS: In the years 2002-2008, 121 consecutive prostate cancer patients underwent radical prostatectomy and postoperative radiotherapy. The median dose was 64 Gy (range: 60-72 Gy). Biochemical and clinical progression-free survival were estimated. Univariate and multivariate analyses were used to analyze clinicopathological variables associated with treatment failure. RESULTS: The median follow-up was 27 months. Three-year bPFS was 72%. On univariate analysis it was influenced by: extracapsular tumor extension (60% vs. 75%, p = 0.0232), seminal vesicles invasion (52% vs. 85%, p = 0.00041), Gleason score ≥ 7 (65% vs. 86%, p = 0.044) and the use of hormonal therapy (50% vs. 80%, p = 0.0058). On multivariate analysis bPFS was associated with: TNM stage (HR = 3.19), postoperative hormonal therapy (HR = 2.6), total irradiation dose (HR = 0.82) and the maximum pretreatment level of prostate-specific antigen (PSA) (HR = 0.95). Three-year cPFS was 84%. On univariate analysis it was influenced by: preoperative PSA level > 10 ng/ml (75% vs. 90%, p = 0.04), vascular-nerve bundles involvement (63% vs. 88%, p = 0.0031), adjacent organs infiltration (50% vs. 85%, p = 0.018) and the use of postoperative hormonal therapy (62% vs. 90%, p = 0.02). On multivariate analysis cPFS was associated with: TNM stage (HR = 2.68), postoperative hormonal therapy (HR = 3.61) and total irradiation dose (HR = 0.78). CONCLUSIONS: Postoperative radiotherapy in patients with unfavorable prognostic factors provides good biochemical and local control. Total irradiation dose and postoperative hormonal therapy are important treatment factors influencing prognosis.

Acute pulmonary embolus in the course of cancer.

Risk of pulmonary embolism (PE) is relatively high in patients with advanced chronic diseases, particularly with malignancies. Most patients with cancer have blood coagulation test abnormalities indicative of up-regulation of the coagulation cascade, increased platelet activation and aggregation. Pulmonary thromboembolism is common in patients with any cancer and incidence is increased by surgery, chemotherapy, radiotherapy and disease progression. Manifestations range from small asymptomatic to life-threatening central PE with subsequent hypotension and cardiogenic shock. Diagnostic algorithms utilizing various noninvasive tests have been developed to determine the pretest probability of PE results of D-dimer assay, chest radiography ECG and computed tomography. The mortality in untreated PE is high (30%) but appropriate treatment may decrease it to 2-18%. The current recommended treatment for massive pulmonary embolus is either thrombolytic therapy or surgical embolectomy.

The side effects of hormonal therapy at the patients with prostate cancer.

Prostate cancer is one of most frequent malignant tumours at men. The androgen-deprivation therapy is the part of cancer treatment. It could be used both in the early stage of prostate cancer and in the bone metastates. From this reason the antiandrogen drugs waste systematically grows. Unfortunately androgen-deprivation therapy has numerous side effects such as: the inferior quality of live, sexual disturbances, the fatigue, the anaemia, the bone mineral density loss and the increase of the risk of breaks the bone, the increase of body mass, insulinresistance, hypercholesterolemia, the increase risk of cardiac disorders. The aim of this article is the introduction of the reader with possibly complications androgen-deprivation therapy and with possibilities in diagnosis and treatment.

Psoriasis exacerbation after hormonotherapy in prostate cancer patient-Case report.

Psoriasis, as the most common inflammatory skin disorder, affects about 2-3% of the world's population. Many non-dermatological conditions have been linked with psoriasis, including cardiovascular diseases, depression, inflammatory bowel disorders, and some cancers, i.e. lung, colon and kidney cancers. Among systemic factors are endocrine and metabolic disturbances as well as many drugs. Erythrodermic psoriasis, the most severe form of the disease, is characterized by diffuse erytrema and scaling, often accompanied by fever, chills, and malaise. A 57-year-old Caucasian man was admitted for curative radiation therapy of adenocarcinoma of the prostate after 3 months of initial hormonal therapy. The management comprised the combined androgen blockade (CAB). On admission the patient reported escalation of psoriasis symptoms, which he had been treated for since 2002. Due to a mild course of the disease he had not required any systemic treatment ever before, even during aggravation periods. The last exacerbation started appearing a month after hormonal therapy implementation. The cutaneous eruptions, already existing, become larger with new foci revealing, mainly on upper and lower limbs. During radiotherapy planning, there appeared a diffuse erythema and scaling on hands and feet with accompanying pruritis. We decided to start the previously planned radiation therapy which included the prostate gland with 1.5 cm margin and provided for the total dose of 72 Gy in 36 fractions. The irradiation was conducted with the four-field technique using a megavoltage linear accelerator. During radiotherapy we photo-documented skin lesions. To our best knowledge hormone therapy (androgen deprivation) of prostate cancer patients has not been reported as an aggravating factor. Thus, the aim of our work is to present the case of a prostate cancer patient who experienced psoriasis exacerbation after implementation of hormonal blockade as a neoadjuvant oncological treatment.

Randomized clinical trial on 7-days-a-week postoperative radiotherapy for high-risk squamous cell head and neck cancer.

PURPOSE: To evaluate the normal tissue reactions and loco-regional control rates (LRC) in patients treated with 7-days-a-week postoperative continuous irradiation (p-CAIR) compared to conventionally fractionated 5-days-a-week postoperative radiotherapy (CF). MATERIALS/METHODS: Between 2001 and 2004, 279 patients with high-risk squamous cell cancer of the larynx (158 pts.) or cancer of the oral cavity/oropharynx (121 pts.) were enrolled. They were stratified according to the primary cancer site (larynx vs. others) and the treating center and randomized to receive 63 Gy in fractions of 1.8 Gy given 5-days-a-week (140 pts: CF) or 7-days-a-week (139 pts: p-CAIR). RESULTS: The acute and late toxicity was considered acceptable, although the proportion of patients with confluent mucositis was higher in p-CAIR compared to CF (60.0 vs. 33.3%). The actuarial 3-year LRC were 64 vs. 70% for CF and p-CAIR, respectively, p=0.32. A statistically significant improvement in 3-year LRC in p-CAIR arm appeared in a subset of the patients with cancer of the oropharynx/oral cavity (74% p-CAIR vs. 53% CF, p=0.02). By contrast, there was no improvement in LRC in a subset of the patients with cancer of the larynx (p=0.46). CONCLUSION: An improvement in LRC attributable to acceleration of postoperative radiotherapy appeared restricted to the patients with cancer of the oropharynx/oral cavity. In patients with cancer of the larynx acceleration of postoperative radiotherapy did not have any beneficial effect.

[The concentration of tissue--type plasminogen activator (t-PA) in extracts of breast cancer tissue]. / Stezenie tkankowego aktywatora plazminogenu (t-PA) w wyciagach tkankowych z raka piersi.

UNLABELLED: Degradation of the extracellular matrix metalloproteinases, which are activated mainly by the plasmin (the key enzyme of the fibrinolysis system), is the basis of the invasion of breast cancer cells. The tissue plasminogen activator (t-PA), a specific serine protease, is one of the plasmin activators. Shifting the balance between factors stimulating and inhibiting angiogenesis within the tumour microenvironment it influences negatively the progression of breast cancer. The aim of the study was to estimate the concentration of t-PA levels in breast cancer tissue extracts in comparison with normal breast tissues as well as to analyze the t-PA level changes in relation to "classical" prognostic factors. MATERIAL AND METHODS: A total number of 30 breast cancer patients aged from 39-79 (mean 58) years entered the study. According to the TNM system the pathological stage of the disease was assessed and the estrogen (ER) and progesterone (PgR) receptor status was determined for each patient. Additionally, in ten patients aged from 29-44 (mean 33) years the level of the t-PA in benign breast tissue lesions was determined. The studied tissues were obtained during surgery. Macroscopically normal tissues, which were located 2 cm from the tumor, served as a controls group. Levels of the t-PA were determined using the enzyme-linked immunosorbent assay (ELISA). RESULTS: The study showed no statistically significant difference between the levels of the t-PA in tumors and in normal tissues. In terms of prognostic factors t-PA level was significantly higher in cancer tissues obtained from patients with no lymph node metastases as well as in tumors containing progesterone receptors. The PgR levels were significantly higher in benign breast lesions in comparison with both, normal tissues and tumors. CONCLUSIONS: The study showed a significant relationship between the high level of t-PA and a favorable prognosis estimated on the basis of "classical" prognostic factors.

Randomized clinical trial on continuous 7-days-a-week postoperative radiotherapy for high-risk squamous cell head-and-neck cancer: a report on acute normal tissue reactions.

BACKGROUND AND PURPOSE: To analyse acute mucosal reactions in patients treated with continuous accelerated postoperative irradiation (p-CAIR) compared to conventionally fractionated postoperative radiotherapy (p-CF). PATIENTS AND METHODS: The patients were randomly assigned to receive 63 Gy in 1.8 Gy fractions 7-days-a-week given over a period of 5 weeks (n=88), or 63 Gy in 1.8 Gy fractions given 5-days-a-week over 7 weeks (n=87). It represents 65% of an overall trial size. Acute mucosal reactions were scored using modified Dische system. Polychotomous logistic regression was used to estimate the influence of the selected variables on maximum grade of mucositis, and percent of the body weight loss during radiotherapy. RESULTS: The average maximum Dische score and percent of the patients with confluent mucositis were higher in patients treated with p-CAIR, compared to p-CF (13.3 vs. 10.8 and 54 vs. 27%). Polychotomous logistic regression analysis revealed that fractionation scheme and tumour site have significantly influenced maximum Dische score. Tumour site (laryngeal vs. other) had even stronger influence on maximum Dische score than fractionation scheme. The average residual Dische score 8 weeks after radiotherapy was higher in p-CAIR compared to p-CF (2.1 vs. 1.4), and was, most frequently, related to persistent mucosal erythema (70 vs. 57% of pts.). No severe consequential toxicity of radiotherapy was observed, so far, in the trial. CONCLUSIONS: While the incidence, intensity and duration of mucosal reactions was higher in p-CAIR than in p-CF the accelerated treatment can be considered tolerable with respect to acute toxicity. In both arms of the trial slight or moderate mucosal erythema was the most frequent acute side effect, which did not completely subside within 8 weeks after irradiation.

Radiotherapy in the prevention of heterotopic ossification after arthroplasty.

Heterotopic ossification (HO) is defined as the formation of mature lamellar bone in nonosseous tissues. HO is a common problem following total hip replacement (THR) and surgical repair of traumatic acetabular fracture (TAF). Without receiving any kind of prophylaxis the incidence of HO in patients with THR is about 30-80%. The etiology of this disorder is not well understood. The treatment of symptomatic HO is excision of heterotopic bone. Radiation therapy is a safe and effective metod for prevention of HO. The present article extensively reviews the clinical studies to define the role of radiotherapy for prevention of HO.