Klaus Kisters

Selenium in the treatment of radiation-associated secondary lymphedema

PURPOSE The aim of this explorative study was to evaluate the impact of selenium in the treatment of lymphedema after radiotherapy. MATERIALS AND METHODS Between June 1996 and June 2001, 12 patients with edema of the arm and 36 patients with edema of the head-and-neck region were treated with selenium for therapy-related lymphedema. Of these 36 patients, 20 had interstitial endolaryngeal edema associated with stridor and dyspnea. All patients received sodium selenite over 4 to 6 weeks. RESULTS Self-assessment using a visual analog scale (n = 48) showed a reduction of 4.3 points when comparing pre- and posttreatment values (p < 0.05). Of 20 patients with endolaryngeal edema, 13 underwent no tracheostomy, 5 underwent a temporary tracheostomy, and only 2 underwent a permanent tracheostomy. Ten of 12 patients with arm edema showed a circumference reduction of the edematous limb and improvement in the Skin-Fold Index by 23.3 points. An improvement of one stage or more was shown by the Földi or the Miller score (n = 28) in 22 (Földi score) and in 24 (Miller score) patients. CONCLUSIONS Treatment with sodium selenite is well tolerated and easy to deliver. Additionally, our results suggest that sodium selenite has a positive effect on secondary-developing lymphedema caused by radiation therapy alone or by irradiation after surgery.

Selenium in Oncology: From Chemistry to Clinics

The essential trace element selenium, which is a crucial cofactor in the most important endogenous antioxidative systems of the human body, is attracting more and more the attention of both laypersons and expert groups. The interest of oncologists mainly focuses in the following clinical aspects: radioprotection of normal tissues, radiosensitizing in malignant tumors, antiedematous effect, prognostic impact of selenium, and effects in primary and secondary cancer prevention. Selenium is a constituent of the small group of selenocysteine-containing selenoproteins and elicits important structural and enzymatic functions. Selenium deficiency has been linked to increased infection risk and adverse mood states. It has been shown to possess cancer-preventive and cytoprotective activities in both animal models and humans. It is well established that Se has a key role in redox regulation and antioxidant function, and hence in membrane integrity, energy metabolism and protection against DNA damage. Recent clinical trials have shown the importance of selenium in clinical oncology. Our own clinical study involving 48 patients suggest that selenium has a positive effect on radiation-associated secondary lymphedema in patients with limb edemas, as well as in the head and neck region, including endolaryngeal edema. Another randomized phase III study of our group was performed to examine the cytoprotective properties of selenium in radiation oncology. The aim was to evaluate whether sodium selenite is able to compensate a preexisting selenium deficiency and to prevent radiation induced diarrhea in adjuvant radiotherapy for pelvic gynecologic malignancies. Through this study, the significant benefits of sodium selenite supplementation with regards to selenium deficiency and radiotherapy induced diarrhea in patients with cervical and uterine cancer has been shown for the first time in a prospective randomized trial. Survival data imply that supplementation with selenium does not interfere with the positive biological effects of radiation treatment and might constitute a valuable adjuvant therapy option especially in marginally supplied individuals. More recently there were emerging concerns coming up from two large clinical prevention trials (NPC, SELECT), that selenium increases the possible risk of developing diabetes type II. Despite obvious flaws of both studies and good counterarguments, a controversial debate remains on the possible advantage and risks of selenium in cancer prevention. However, in the light of the recent clinical trials the potential benefits of selenium supplementation in tumor patients are undeniable, even if further research is needed.

Multicenter, Phase 3 Trial Comparing Selenium Supplementation With Observation in Gynecologic Radiation Oncology

PURPOSE We assessed whether adjuvant supplementation with selenium improves the selenium status and reduces side effects of patients treated by radiotherapy (RT) for cervical and uterine cancer. METHODS AND MATERIALS Whole-blood selenium concentrations were measured in patients with cervical cancer (n = 11) and uterine cancer (n = 70) after surgical treatment, during RT, at the end of RT, and 6 weeks after RT. Patients with initial selenium concentrations of less than 84μg/L were randomized before RT either to receive 500 μg of selenium (in the form of sodium selenite [selenase, biosyn Arzneimittel GmbH, Fellbach, Germany]) by mouth on the days of RT and 300 μg of selenium on the days without RT or to receive no supplement during RT. The primary endpoint of this multicenter Phase 3 study was to assess the efficiency of selenium supplementation during RT; the secondary endpoint was to decrease radiation-induced diarrhea and other RT-dependent side effects. RESULTS A total of 81 patients were randomized. We enrolled 39 in the selenium group (SG) and 42 in the control group (CG). Selenium levels did not differ between the SG and CG upon study initiation but were significantly higher in the SG at the end of RT. The actuarial incidence of diarrhea of Grade 2 or higher according to Common Toxicity Criteria (version 2) in the SG was 20.5% compared with 44.5% in the CG (p = 0.04). Other blood parameters, Eastern Cooperative Oncology Group performance status, and self-reported quality of life were not different between the groups. CONCLUSIONS Selenium supplementation during RT is effective in improving blood selenium status in selenium-deficient cervical and uterine cancer patients and reduces the number of episodes and severity of RT-induced diarrhea.

Selenium or No Selenium— That Is the Question in Tumor Patients: A New Controversy

The essential trace element selenium, which is a crucial cofactor in the most important endogenous antioxidative systems of the human body, is attracting more attention from both laypersons and expert groups. The interest of oncologists mainly focuses on the following clinical aspects: protection of normal tissues, sensitizing in malignant tumors, antiedematous effect, prognostic impact of selenium, and effects in primary and secondary cancer prevention. Selenium is a constituent of the small group of selenocysteine-containing selenoproteins and elicits important structural and enzymatic functions. Selenium deficiency has been linked to increased infection risk and adverse mood states. It has been shown to possess cancer-preventive and cytoprotective activities in both animal models and humans. It is well established that it has a key role in redox regulation and antioxidant function, and hence in membrane integrity, energy metabolism, and protection against DNA damage. Recent clinical trials have shown the importance of selenium in clinical oncology. In 2009, a significant benefit of sodium selenite supplementation—with no protection of tumor cells, which is often suspected by oncologists— was shown in a prospective randomized trial in gynecologic cancer patients undergoing radiation therapy. More recently, concerns arose from 2 large clinical prevention trials (NPC, SELECT) that selenium may increase the risk of developing type 2 diabetes. Despite obvious flaws in both studies and good counterarguments, controversy remains on the possible advantages and risks of selenium in cancer prevention. However, in the light of the recent clinical trials the potential benefits of selenium supplementation in tumor patients are becoming obvious, even though further research is needed.

Whole blood selenium levels (WBSL) in patients with prostate cancer (PC), benign prostatic hyperplasia (BPH) and healthy male inhabitants (HMI) and prostatic tissue selenium levels (PTSL) in patients with PC and BPH

Background. The aim of this exploratory study was to evaluate whether significant differences exist between whole blood selenium levels (WBSL) in patients with prostate cancer (PC), benign prostatic hyperplasia (BPH), healthy male inhabitants (HMI) in northern Bavaria and the normal value. Furthermore, we investigated whether differences exist between prostatic tissue selenium levels (PTSL) in patients with PC, BPH and the benign tissue surrounding the PC. Material and methods. We prospectively evaluated WBSL in 24 patients with PC, 21 patients with BPH, and 21 HMI. Measurements of PTSL were performed in 17 patients with PC and 22 patients with BPH. In 9 cases with PC, measurements were also done in the benign tissue surrounding the carcinoma. Measurements were performed using automated graphite furnace atomic absorption spectrophotometry. Results. In patients with PC, there is a significantly lower WBSL in comparison to HMI (p=0.04). There is no significant difference in WBSL between BPH-patients and HMI (p=0.13) and between PC- and BPH-patients (p=0.67). In all patients and the HMI, there is a significantly lower WBSL in comparison to the recommended normal value of 85 – 162 µg/l (p<0.01). There is no significant difference in PTSL between PC and BPH (p=0.49), and between PC and the tissue compartment surrounding the PC (p=0.56). PTSL seemed to be reduced in the compartment surrounding the PC in comparison to BPH (p=0.03). In PC-patients, there is no significant correlation between WBSL and prostate specific antigen (PSA) (?=−0.20; p=0.36), Gleason score (?=0.32, p=0.13), and T-stage (?=0.22; p=0.23). Conclusion. Since the WBSL measured in all men with PC and BPH, and in HMI participating in our study were significantly lower than the recommended normal range, our findings may support the recommendation of selenium supplementation.

Hyperkalzämie am Lebensende

Problem: Die Entgleisung des Elektrolythaushaltes gilt als prognostisch ungunstiges Zeichen bei Patienten mit fortgeschrittenen Tumorleiden. Wann ist eine Hyperkalzamie am Lebensende wirklich behandlungsbedurftig? Material und Methode: Zwischen 1.1.2014 und 31.7.2014 registrierten wir 9 Patienten, die wegen dem Leitbild einer Verwirrtheit und Bewusstseinseintrubung und einer exzessiven Hyperkalzamie stationar aufgenommen wurden. Die deskriptiv-retrospektive Analyse dieser Patienten erfolgt in kasuistischer Form. Ergebnisse: Alle Patienten hatten keine Hirnmetastasen (MRT-Befund). Alle Patienten wiesen Serum-Kalziumspiegel > 2,7 mmol/l auf. Klinisch boten ebenfalls alle Patienten eine Verwirrtheit und Halluzinationen mit passageren Aggressionen. Die Anamnesezeit der psychiatrischen Veranderungen war kurz ( Therapeutisch erhielten diese Patienten Bisphosphonate und Midazolam IV. Sofern es zu einer Besserung der Hyperkalzamie kam, konnte die Sedierung beendet werden, die Patienten klarten auf und wurden entlassen (3/9 Patienten). Sechs Patienten verstarben vorher an einem Multiorganversagen bei onkologischem Grundleiden, einer nach Entlassung. Schlussfolgerung: Psychotische Reaktionen ohne Hirnmetastasierung sollten bei Palliativpatienten an eine Hyperkalzamie denken lassen, deren Therapie dann aus Bisphosphonaten und einer passageren palliativen Sedierung besteht.

Bedeutung der Elektrolyte in der Onkologie

THE ROLE OF ELECTROLYTES IN ONCOLOGY. Hitherto, hardly any research has been carried out regarding the role of the electrolytes sodium, potassium, calcium and magnesium in oncology. Similarly, chloride and phosphate have received very little attention. Based on the numerous clinical studies and observations, the changes in the electrolyte household in oncological patients have nonetheless become more significant. Therefore, this article specifically looks at the clinical importance of the electrolytes sodium, potassium, calcium and magnesium.