Evaluation of the efficacy and toxicity profile associated with intraperitoneal chemotherapy use in older women.

OBJECTIVE: Intraperitoneal (IP) chemotherapy (CT) for treatment of epithelial ovarian cancer (EOC) has been shown to provide a substantial OS advantage. This study aims to compare the toxicity and benefits of IP CT in patients ≥70 with those <70. METHODS: We performed a single institution retrospective review of patients diagnosed with Stage IIA-IIIC EOC from 2000 to 2013 who received IP CT. Clinicopathologic characteristics were extracted, and survival was calculated. RESULTS: 133 patients were included with 100 pts. <70years old and 33 pts. ≥70years old. Clinical trial enrollment was similar despite age. In trial enrolled patients, older patients received statistically fewer cycles of therapy (6.4 vs 5.8, p=0.002) but had similar dose delays (0.9 vs 0.7, p=0.72), and modifications (0.9 vs 0.36, p=0.11). Median PFS (27 vs 31months) and OS (71 and 62months) were not statistically different. Grade 3/4 neutropenia was significantly worse in the older patients (82% vs 100%, p=0.04). Neuropathy grade ≥2 and other non-hematologic toxicities were not different between age groups. CONCLUSIONS: Despite completing fewer cycles of IP CT, older EOC patients had comparable survival to younger patients. The population of older patients receiving IP CT in this study were on clinical trial and likely to be heartier than the general older population. IP CT appears well tolerated and effective among select older patients and is likely under-utilized outside of clinical trials.

NF-κB/p65 expression before and after treatment in rectal cancer patients undergoing neoadjuvant (chemo)radiotherapy and surgery: prognostic marker for disease progression and survival.

Nuclear factor-kappaB (NF-κB), especially p65 subunit, has been associated with origin and progression of cancer as well as with the resistance to radiotherapy and chemotherapy in experimental models. The aim of the present study was to determine expression of NF-κB/p65 in tumor specimens before and after treatment of rectal cancer patients and to evaluate possible relationship between expression of NF-κB/p65 before and after (chemo)radiotherapy, other tumor characteristics and the clinical outcome. Furthermore, NF-κB/p65 was studied in relationship to pathologic response to preoperative (chemo)radiotherapy. Fifty patients with rectal cancer undergoing neoadjuvant (chemo)radiotherapy and surgery were included in the study. Pre-treatment rectal cancer specimens were obtained from diagnostic colonoscopy. Post-treatment rectal cancer specimens were obtained from surgically removed part of the rectum with the tumor. NF-κB/p65 expression was determined by immunohistochemistry and analysis was performed both in biopsies and in post-treatment tumor samples. Cytoplasmic positivity in tumor cells and nuclear positivity in lymphocytes were detected. High NF-κB/p65 positivity in pre-treatment tumor samples was significantly associated with shortened overall survival (OS). Disease-free survival (DFS) tends to be shortened as well. In post-treatment tumor samples, high NF-κB/p65 positivity was neither associated with shortened OS nor with shortened DFS. In post-treatment samples residual tumor cells deeply infiltrating the wall of the rectum with high NF-κB/p65 expression were found. The cells were linked to significantly worse clinical outcome in terms of shortened OS and DFS. NF-κB/p65 positivity did not correlate with pathologic response to preoperative (chemo)radiotherapy. In conclusion, our data suggest that high level of NF-κB/p65 subunit may be associated with more aggressive features of the tumor, higher metastatic potential, and shortened overall survival, but it does not correlate with resistance to (chemo)radiotherapy. Consequently, the level of NF-κB/p65 may help to select those patients who have poor prognosis and are candidates for more intensive anticancer therapy. For these purposes both pre-treatment and post-treatment tumor samples may be used.

[Influence of preoperative chemoradiotherapy on changes of epidermal growth factor receptor expression in patients treated by preoperative chemoradiotherapy for local advanced rectal carcinoma]. / Vliv predoperacní chemoradioterapie na zmenu exprese receptoru pro epidermální rustový faktor u pacientu lécených predoperacní chemoradioterapií pro lokálne pokrocilý karcinom rekta.

AIM: The aim of this retrospective study was to determine the prognostic impact of expression of epidermal growth factor receptor (EGFR) changes during neoadjuvant chemoradiotherapy in patients with locally advanced rectal adenocarcinoma. MATERIAL AND METHODS: One hundred and three patients with locally advanced rectal adenocarcinoma of stage II and III were evaluated. All patients were administered the total dose of 44 --  50.4 Gy. Concomitantly, the patients received capecitabine in the dose 825 mg/ m² in two daily oral administrations or 5- fluorouracil in the dose 200 mg/ m² in continuous infusion. Surgery was indicated at intervals of 4-8 weeks from chemoradiotherapy completion. EGFR expression in the pretreatment biopsies and in resected specimens was assessed with immunohistochemistry. RESULTS: All of 103 patients received radiotherapy without interruption up to the total planned dose. Downstaging was described in 64 patients. Six patients had complete pathologic remission. Recurrence occurred in 49 patients. Local recurrence was found in 22 patients, generalization of disease was reported in 27 patients. A total of 51 patients died. Increased EGFR expression was found in 26 patients. The statistically significantly shorter overall survival (p < 0.001) and disease-free survival (p < 0.001) was found in patients with increased expression of EGFR compared with patients where no increase in the expression of EGFR was observed during neoadjuvant chemoradiotherapy. CONCLUSIONS: The overexpression of EGFR during neoadjuvant chemoradiotherapy for locally advanced rectal adenocarcinoma is associated with significant shorter overall survival and disease-free survival.

[The combination of neoadjuvant chemoradiotherapy and epidermal growth factor receptor inhibitors in the treatment of rectal adenocarcinoma]. / Neoadjuvantní chemoradioterapie karcinomu rekta v kombinaci s inhibitory receptoru pro rustový epidermální faktor.

Rectal adenocarcinoma, in contrast to colorectal carcinoma, is typical of its high local reccurence rate. Radiotherapy is proved to reduce the incidence of recurrences. Neoadjuvant chemoradiotherapy demonstrated better treatment results than adjuvant chemoradiotherapy. Standard cytotoxic agents involved in combination therapy are 5- flurouracil or capecitabin. Epidermal growth factor receptor (EGFR) is supposed to play an important role in cell- cycle regulation, proliferation, differentiation, and surviving of normal epithelial tissues. EGFR overexpression in patients with rectal adenocarcinoma is associated with radioresistance of malignant tissues, lower rates of patological complete response after neoadjuvant chemoradiation and generally poor survival. There are many clinical studies describing combination of neoadjuvant chemoradiotherapy with EGFR inhibitors, however, this regimen has not gained an acceptance as a standard of treatmentment.

Executive summary: Football for health - prevention and treatment of non-communicable diseases across the lifespan through football.

This supplement contains 16 original articles describing how football conducted as small sided games affects fitness and health of untrained individuals across the lifespan. The intermittent nature of football and high exercise intensity result in a broad range of effects. The heart changes its structure and improves its function. Blood pressure is markedly reduced with the mean arterial blood pressure being lowered by ~10 mmHg for hypertensive men and women training 2-3 times/week for 12-26 weeks. Triglycerides and cholesterol are lowered and body fat declines, especially in middle-aged men and women with type 2 diabetes. Furthermore, muscle mass and bone mineral density increases in a number of participant groups, including 65-75-year-old men. The functional capacity is elevated with increases in VO2 max of 10-15%, and 50-100% improvements in the capacity to perform intermittent work within 16 weeks. These effects apply irrespective of whether the participants are young, overweight, elderly or suffering from a disease. The studies clearly show that the participants enjoy playing football and form special relationships with their team mates. Thus, football is a healthy activity, providing a unique opportunity to increase recruitment and adherence to physical activity in a hitherto underserved population, and to treat and rehabilitate patients with hypertension, type 2 diabetes and prostate cancer.

Practical experience with the implementation of an athlete's biological profile in athletics, cycling, football and swimming.

The introduction of the athlete's biological passport (ABP) has been a milestone in the fight against doping. The ABP is a collection of measurements of different biological parameters influenced by the administration of doping agents through the time and for each athlete. Two different modules have been developed and validated so far: the haematological module, which aims to identify enhancement of oxygen transport, including use of erythropoiesis-stimulating agents and any form of blood transfusion or manipulation, which became effective in 2010; and the steroidal module, which intends to detect the use of endogenous anabolic androgenic steroids when administered exogenously and other anabolic agents, which was introduced in 2014. Prior to the implementation of the haematological module, it is important to define an athlete's testing pool on whom to collect blood and/or urine in-competition and out-of-competition (for the steroidal module, this is irrelevant because all collected urine samples will be subjected to analysis for the steroidal variables) and to be compliant with the strict requirements of the World Anti-Doping Agency ABP Operating Guidelines. The established individual profile can be used either to target traditional antidoping tests (recombinant erythropoietins, or homologous blood transfusion tests for the haematological module; isotope ratio mass spectrometry (IRMS) for the steroidal module) or to support an antidoping rule violation due to the use of a forbidden substance or method. In this article, we present the experience of four major International Federations which have implemented an ABP programme, focusing on the haematological module. They constitute examples which could be followed by other antidoping organisations wishing to introduce this new, efficient and innovative antidoping tool.

Towards an outcome documentation in manual medicine: a first proposal of the International Classification of Functioning, Disability and Health (ICF) intervention categories for manual medicine based on a Delphi survey.

AIM: The International Classification of Functioning, Disability and Health (ICF) provides a useful framework for the comprehensive description of the patients' functional health. The aim of this study was to identify the ICF categories that represent the patients' problems treated by manual medicine practitioners in order to facilitate its application in manual medicine. This selection of ICF categories could be used for assessment, treatment documentation and quality management in manual medicine practice. METHODS: Swiss manual medicine experts were asked about the patients' problems commonly treated by manual medicine practitioners in a three-round survey using the Delphi technique. Responses were linked to the ICF. RESULTS: Forty-eight manual medicine experts gave a total of 808 responses that were linked to 225 different ICF categories; 106 ICF categories which reached an agreement of at least 50% among the participants in the final Delphi-round were included in the set of ICF Intervention Categories for Manual Medicine; 42 (40%) of the categories are assigned to the ICF component body functions, 36 (34%) represent the ICF component body structures and 28 (26%) the ICF component activities and participation. CONCLUSION: A first proposal of ICF Intervention Categories for Manual Medicine was defined and needs to be validated in further studies.

The use of medication and nutritional supplements during FIFA World Cups 2002 and 2006.

OBJECTIVE: To examine medication use in male top-level football players prior to and during international tournaments. DESIGN: Prospective survey. MATERIAL: 2944 team physicians' reports on players' medication intake. METHODS: Each team physician was asked to document all medication and nutritional supplements taken in the 72 h prior to each match. RESULTS: A total of 10,384 substances were reported (1.8 substances/player/match); 4450 (42.9%) of these were medicinal and 5934 (57.1%) nutritional supplements. The medications prescribed most frequently were non-steroidal anti-inflammatory agents (n = 2092; 20.1%); more than half of the players took these at least once during a tournament and more than 10% prior to every match (156 out of 1472). Beta-2-agonists were reported for 1.4% (n = 20) and inhaled corticosteroids for 1.6% (n = 23) of participating players. Injected corticosteroids were reported for 73 players. CONCLUSIONS: The high intake of medication in international football--especially of non-steroidal anti-inflammatory drugs--is alarming and should be addressed. The results raise questions as to whether the medication was taken solely for therapeutic reasons. In view of the potential side effects, more restrictive recommendations for sport need to be developed.

[The molecular screening of the stool for the colorectal carcinoma]. / Molekulární screening stolice pro kolorektální karcinom.

BACKGROUND: Current screening methods of colorectal carcinoma are based on examination of occult bleeding in the stool, and further on endoscopic and irrigographical (barium enema) examinations. Population-based non-invasive screening method having high sensitivity and specificity is needed. METHODS: Detection of molecular alterations in colonocytes from the stool may be a promising new diagnostic tool for such screening. Determination of mutations in APC, K-ras, DCC, p53 genes and "long" DNA may serve for early detection of colorectal cancer from stool samples. Multi-target DNA-assays employing all these markers suggest high sensitivity and specificity, unfortunately also expensiveness. Therefore finding a marker characteristic for all tumor cells would be desirable. Nuclear faktor-kappaB (NF-kappaB) could be such marker suitable for determination in colonocytes shed into the stool. CONCLUSION: Molecular testing of stool for early detection of colorectal cancer may be a promising screening method for this disease. Large multicenter trials are required to validate results obtained from preliminary clinical studies.

[Surgical treatment of late tractional retinal detachment appearing on the basis of retinopathy of prematurity]. / Chirurgická lécba pozdního trakcního odchlípení sítnice vzniklého na podklade retinopatie nedonosených.

Retinopathy of prematurity (ROP) is a proliferative retinopathy affecting predominantly immature children and children with low birth weight under 2500 g in 5-6%. During 11 years we operated on 15 eyes of 15 patients aged 5-31 years, because of late tractional retinal detachment (TRD) appearing on the basis of ROP. The average follow-up period was 37.2 months; the minimal follow-up period was 1 year. In all patients, the personal medical history revealed the pre-term birth at the gestation age of 28-34 weeks. The birth weight was in the range 850-1600 grams. According to the extend of vitreoretinal traction and type of retinal defect we indicated: a) primary cryosurgical procedure (CP) with episcleral silicone implants. The operation was indicated in 6 eyes: cerclage, segmental perilimbal plombage in the temporal half and puncture of the subretinal fluid; b) pars plana vitrectomy (PPV). In total in 9 eyes the PPV was indicated, in 5 eyes it was supplemented with relaxing retinotomy, and in 7 eyes with silicone oil (SO) implantation. Three eyes were re-operated by means of PPV with SO implantation. The final anatomical success of the surgical treatment of the prognostic unfavorable TRD, including re-operations was achieved in 12 eyes (80%), which we consider as a good one. The visual acuity improved or remained the same also in 12 eyes (80%) and visual acuity 6/60 and better (20/200 or 0.1) in 8 out of 15 eyes (53%).

Weekly paclitaxel combined with local hyperthermia in the therapy of breast cancer locally recurrent after mastectomy--a pilot experience.

BACKGROUND: The combination of chemotherapy and hyperthermia (HT) is a promising approach in the treatment of malignant tumors. In the present report we evaluate the efficacy and toxicity of a combination of weekly paclitaxel combined with local hyperthermia in breast cancer. PATIENTS AND METHODS: 7 patients were treated for inoperable local recurrence of breast cancer after mastectomy, irradiation, and chemotherapy or hormonal therapy. They weekly received paclitaxel (60-80 mg/m(2)) in 3-h infusions followed by local HT 41-44 degrees C for 45 min for 6-18 cycles. RESULTS: Objective local response was observed in all treated patients (complete response in 4 patients and partial response in 3 patients). There were no grade 3 or 4 toxicities, neurologic toxicity or hypersensitivity reactions. Local tolerance to this regimen was also good, with only 4 patients developing mild transient erythema. CONCLUSION: Our experience indicates that the combination of weekly paclitaxel and HT may be effective in the treatment of locally recurrent breast cancer after mastectomy.

Liposomal doxorubicin combined with regional hyperthermia: reducing systemic toxicity and improving locoregional efficacy in the treatment of solid tumors.

Incorporation of doxorubicin into polyethylene glycol-coated (pegylated) liposomes increases the therapeutic index, prolongs circulation time and enhances tumor localization. Pegylated liposomal doxorubicin (PLD) is an established therapeutic agent in epithelial ovarian carcinoma (EOC), breast carcinoma or Kaposi's sarcoma, and PLD administration results in reduction of toxicity. Addition of regional hyperthermia increases liposome extravasation, induces the doxorubicin release from the liposomes, and the combination of hyperthermia and doxorubicin itself may be supra-additive, resulting in enhanced antitumor efficacy in the heated region. Encouraging results have been reported for the combination of PLD and hyperthermia in EOC, breast carcinoma and hepatocellular carcinoma.

Pegylated liposomal doxorubicin in combination with hyperthermia for treatment of skin metastases of breast carcinoma: a case report.

BACKGROUND: Incorporation of doxorubicin hydrochloride into pegylated liposomes (PLD) may decrease chemotherapy side effects and increase the activity. Hyperthermia could further potentiate its effectiveness. CASE REPORT: A patient with skin metastases of breast carcinoma was treated with intravenous infusion of PLD (Caelyx) in combination with ultrasound hyperthermia. Each cycle consisted of infusion of 40 mg PLD absolute dose, followed by 2 fractions of hyperthermia 41-43 degrees C for 45 min 1 and 48 h after infusion. A complete remission was observed after the combination treatment with no significant toxicity. CONCLUSION: Present observations suggest that the combination of PLD with hyperthermia of skin metastases of breast carcinoma may be an active and well tolerated treatment.

Endovascular brachytherapy potentiated by hyperthermia in the prevention of vascular restenosis. A case report.

BACKGROUND: The combination of hyperthermia and radiotherapy has additive or synergistic effects. This combination has been studied extensively in radiation oncology, but not in the prevention of vascular restenosis. CASE REPORT: A patient with restenosis of cephalic vein underwent percutaneous transluminal angioplasty (PTA) followed by endovascular irradiation with 192Iridium (12 Gy) using a high dose rate afterloading technique. After endovascular irradiation, one fraction of external ultrasound hyperthermia was administered to the irradiated segment. There was no restenosis in the treated vessel segment according to duplex sonography performed 192 days after treatment. No radiation or hyperthermia associated side effects were observed. CONCLUSIONS: Present observations suggest that endovascular brachytherapy of restenosis potentiated by hyperthermia is a technically feasible and well-tolerated treatment. The additive and synergistic effects of hyperthermia, in conjunction with radiation, could be of benefit in the prevention of vascular restenosis.

[Phytotherapeutic aspects of diseases of the circulatory system. 6. Leuzea carthamoides (WILLD.) DC: the status of research and possible use of the taxon]. / Fytoterapeutické aspekty onemocnení obehového systému. 6. Leuzea carthamoides (WILLD.) DC.: stav výzkumu a moznosti vyuzití taxonu.

Leuzea carthamoides (WILLD.) DC., Asteraceae, has become an important taxon usable in human practice and animal production in recent years. Originally an endemic plant of southern Siberia, now it is widely grown not only in the Union of Independent States, once the original region of introduction, but also in central and eastern Europe. The principal constituents of the whole plant are ecdysteroids (5 beta-cholest-6-on-7-ene derivatives) and flavonoids. In addition, the aerial part contains sesquiterpenic lactones of the guajanolide type, and the roots contain polyines (on the thiophene base). The present paper comprehensively discusses the occurrence, content and biological activity of these substances, the preparations manufactured from the plant, their use in therapeutic practice, food manufacture and animal production in the world and the Czech Republic. The plant has certainly become a taxon with prospects in the Czech Republic, particularly as the source of 20-hydroxyecdysone, which is getting into the limelight in the world.

[Functional treatment of diseases and injuries of the cervical spine]. / Die funktionelle Behandlung der Erkrankungen und Verletzungen der Halswirbelsäule.

The clinical findings and pain symptoms determine the functional treatment of the cervical spine disorders. Acute pain syndromes are to be approached by passive procedures, such as massage, electrotherapy, trigger point treatment. Could the pain reaction be reduced, the mobilizing techniques, including manipulation are indicated, followed by training therapy/reconditioning of shoulder girdle muscles. The patients are also to be instructed to perform home exercise program aiming the stabilization of cervical spine.

[The functional treatment of cervical spine disorders and trauma]. / Die funktionelle Behandlung der Erkrankungen und Verletzungen der Halswirbelsäule.

The clinical findings and pain symptoms determine the functional treatment of the cervical spine disorders. Acute pain syndromes are to be approached by passive procedures, such as massage, electrotherapy, trigger point treatment. Could the nocireaction be reduced, the mobilizing techniques, including manipulation are indicated, followed by trainingtherapy/reconditioning of shoulder girdle muscles. The patients are also to be instructed to perform home exercise program aiming the stabilization of cervical spine.

[The effect of ionizing irradiation on sensory changes in feed in relation to their utilization by dogs]. / Vliv ionizujícího zárení na senzorické zmeny krmiv ve vztahu k jejich vyuzitelnosti psy.

To evaluate the effect of ionizing radiation on sensory changes of feeds in relation to their utilization by dogs, four groups of experimental animals were formed. Two groups were fed a ration where the main component (meat feed mixture VETACAN and loose feed mixture VETAVIT) was irradiated by radioisotope Co 60 at the dose of 25 kGy/kg for the period of 90 days. In the remaining two groups a non-irradiated ration was used for the same period. For both diets, control groups of dogs were formed and the feed ration was biologically fortified by a vitamin-mineral supplement to the physiological standard. It followed from the observations that the effect of radiation caused a significant qualitative decrease in the level of energy nutrients, particularly in the protein and lipid sphere. It is assumed that the extent of damage of lipid fraction is also accompanied by deficient vitamin activity and further by significant changes of taste and aromatic properties felt by animals. Irradiation of the feed ration caused a significant 20 to 25% decrease of food intake with a subsequent decrease of live weight and deterioration of physical condition. Irradiated diets without biological fortification caused significant losses of weight from the initial value mean = 39.5 kg to mean = 35.33 kg, in comparison with the non-irradiated rations through which the live weight was stabilized, and at biological fortification positively influenced. Irradiation of the feed ration during the period of study had not caused a response of the organism displayed in changes of physiological values of body temperature and heart and respiration rates in experimental animals. Radiosterilization of feeds had not caused any significant decrease of training ability and performance of dogs.

[The effect of feeds treated with ionizing irradiation on biochemical indicators of the nutritional value of energy nutrients]. / Vliv krmiv osetrených ionizujícím zárením na nekteré biochemické ukazatele úrovne výzivy v oblasti energetických zivin.

The influence of feedstuffs treated with ionizing radiation on the nutrition of dogs was tested in four groups of animals. Two groups were administered for 90 days a ration, the main part of which (VETACAN meat feed mixture and VETAVIT loose feed mixture) was irradiated with radioisotope Co 60 of the intensity of 25 kGy/kg, in other two groups of dogs the nonirradiated ration was used for the same time period. The control groups of dogs were put together for these two diets. The laboratory examination of irradiated feedstuffs confirmed their complete microbiological and mycological intactness. However, the irradiation brought about a significant 35% degradation of essential amino acids with an increase of ammonia nitrogen, destructive changes in the lipid component of feedstuffs and a partial decomposition of the saccharide part of the VETAVIT feed mixture, expressed by the acidity of water extract. The sensory evaluation of irradiated feedstuffs did not show any perceptible alterations. The haematological examination of the blood of animals, which had been administered irradiated feed rations, demonstrated a significant negative influence on the blood picture. The biochemical examination of the blood serum and plasma revealed that total proteins of experimental dogs dropped and the creatinine level was also significantly decreased. Neither was the level of carbohydrate nutrition nor the energy saturation affected by irradiation. The glucose levels in the blood serum of dogs fluctuated within the range of physiological reference values. The growth of free ammoniacal bases of feedstuffs, evoked by ionizing radiation, conditioned obviously the level of actual pH of blood in dogs as determined in this study. The destruction of lipoid fraction in the feedstuffs induced a decrease in the activity of lipophile retinol and thus the biological value of feeds was impaired. The biochemical examination of ALT, AST and ALP enzyme activity did not show any increased activity of parenchyma, in particular of liver cell. A decisive role of the biological quality of feed ration for utilization of some minerals was demonstrated by a significant decrease of the magnesium level in animals administered irradiated feed rations without any biological supplementation. On the contrary, the potassium, calcium and phosphorus levels did not reflect this dietary difference between the groups.