Management of extravasation of oxaliplatin by mimicking its biotransformation

Although oxaliplatin (Oxali) plays a key role in the treatment of many types of cancer and has been reported to be an irritant, there is no specific and effective method for its extravasation and failure in Oxali extravasation management results in the need for plastic surgery. In the body, Oxali bio-transforms upon dilution in chloride-containing buffer salts to its di-chloro derivative and loses an oxalate molecule. Consequently, the chloride ions exchange with water molecules in the intracellular environment to produce the di-aqua derivative, which is the most active biotransformation product of Oxali in terms of forming the DNA adducts. Thus, inhibiting transformation of di-chloro to di-aqua derivatives by accumulating chloride ions at the site of extravasation and saturating the Oxali molecule with these ions is a strategy that could help manage extravasation. Injecting normal saline at this site is a simple yet effective way to achieve this goal

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Management of extravasation of oxaliplatin by mimicking its biotransformation.

Although oxaliplatin (Oxali) plays a key role in the treatment of many types of cancer and has been reported to be an irritant, there is no specific and effective method for its extravasation and failure in Oxali extravasation management results in the need for plastic surgery. In the body, Oxali bio-transforms upon dilution in chloride-containing buffer salts to its di-chloro derivative and loses an oxalate molecule. Consequently, the chloride ions exchange with water molecules in the intracellular environment to produce the di-aqua derivative, which is the most active biotransformation product of Oxali in terms of forming the DNA adducts. Thus, inhibiting transformation of di-chloro to di-aqua derivatives by accumulating chloride ions at the site of extravasation and saturating the Oxali molecule with these ions is a strategy that could help manage extravasation. Injecting normal saline at this site is a simple yet effective way to achieve this goal.

Temperature measurements in a capacitive system of deep loco-regional hyperthermia.

Hyperthermia has been shown to be a medically useful procedure applicable for different indications. For the connection between clinical effects and heat, it is important to understand the actual temperatures achieved in the tissue. There are limited temperature data available when using capacitive hyperthermia devices even though this is worldwide the most widespread method for loco-regional heating. Hence, this study examines temperature measurements using capacitive heating. Bioequivalent phantoms were used for the measurements, which, however, do not consider perfusion in live tissue. In general, the required temperature impact for an effective cancer therapy should need an increase of 0.2°C/min, which has been achieved. In the described tests on the non-perfused dummy, on average, the temperature increases by approximately 2°C in the first 12 min. The temperature difference relative to the starting temperature was 10-12°C within a therapy time of 60 min (rising from the initial room temperature between 20-24°C and 32-34°C). The average deviation with three individual measurements each on different days in a specified localization was 2°C. The minimum temperature difference was 4.2°C, and the maximum value was reached in the liver with 10.5°C. These values were achieved with a moderate energy input of 60-150 watts, with much higher performance outputs still available. These results show that the tested capacitive device is capable of achieving quick temperature increase with a sufficient impact into the depth of a body.

Successful treatment of c-kit-positive metastatic Adenoid Cystic Carcinoma (ACC) with a combination of curcumin plus imatinib: A case report.

Adenoid cystic carcinoma (ACC) is an aggressive malignant neoplasm of the secretory glands. Conventional chemotherapy has poor effectiveness against metastatic ACC. Thus, a novel effective therapy is needed against metastatic ACC. A majority of ACCs (up to 94%) express c-kit. Imatinib is monoclonal antibody with specific activity against c-kit but has not been found to be effective in treating patients with ACC in which c-kit is overexpressed and activated. The NF-κB and mTOR pathways have been shown that ubiquitously and concurrently activated, indicating that the inhibition of these pathways may represent a novel treatment approach for patients with ACC. Curcumin has been shown to inhibit NF-κB and NF-κB-related pathways. 43-year-old patient was diagnosed ACC from submandibular salivary gland. After complete resection of tumor adjuvant radiotherapy was initiated. Seven years later multiple lung metastases were detected and ACC was confirmed by re-biopsy. First-line chemotherapy failed. NF-κB and c-kit were overexpressed in the metastatic specimens. Therefore, we treated the patient with metastatic chemoresistant ACC with imatinib 400mg/day and intravenous curcumin 225mg/m(2) twice a week plus oral bioavailable curcumin Arantal(®) 2×84mg/day. At 24 months, we observed near complete anatomic and complete metabolic response. To our knowledge, this is the first report of a patient with a c-kit-positive ACC that is successfully treated with the combination of imatinib and curcumin in an integrative approach.

No harmful effect of mycophenolate mofetil on liver regeneration: an experimental study.

AIM: The aim of this experimental study was to examine the effects of mycophenolate mofetil (MMF) on liver regeneration in a partial hepatectomy model. METHODS: Rats were divided into 3 groups immediately following partial liver resection: saline, controls intraperitoneally (MMF; Group 1); MMF (15 mg/kg/d; Group II), and MMF (30 mg/kg/d; Group III). On days 3 and 7 following liver resection we humanely killed half of the rats in each group to measure alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and to evaluate Ki-67 using immunohistochemistry. We calculated liver regeneration rates. RESULTS: The difference between ALT levels on days 3 and 7 was not significantly different among the groups (P = .157; P = .292; P > .05, respectively). The AST levels were significantly different at 3 days (P = .018) but not 7 days (P = .385). The Ki-67 level were different among groups at day 3 (P = .002) but not at day 7 (P = .290). Liver regeneration rates were not different among the groups either at 3 or at 7 days (P = .264 and P = .925, respectively). CONCLUSION: MMF stimulates mitosis but its effect on regeneration is not clear. MMF appeared to show no adverse effects on liver regeneration.

Therapy, outcome and analysis of c-kit expression in patients with extrapulmonary small cell carcinoma.

In this study, we aimed to investigate the clinicopathological characteristics with special emphasis on c-kit expression and the treatment results of patients with extrapulmonary small cell carcinoma (EPSCC). The medical records of the patients with EPSCC were reviewed, and the data regarding patient and tumour characteristics, treatment and clinical outcome were retrieved and analysed. A total of 28 patients with the diagnosis of EPSCC were identified. There were 19 males and 9 females, with a mean age of 56.5 years. Patients with limited disease (LD) (n = 13) were treated with surgery, chemotherapy (CT) and radiotherapy with different sequences. Patients with extensive disease (ED) (n = 15) were mainly treated with combination CT. The median overall survival was 14.5 months in patients with LD compared to 11 months in those with ED (p = 0.029). Ten patients (36%) showed c-kit overexpression. There was no significant difference between the survival of c-kit-positive and c-kit-negative patients (p = 0.367). In conclusion, our study demonstrates that the prognosis of EPSCC is poor despite currently available treatments. C-kit may be considered as a potential target for novel therapeutical approaches.

Comparison of the serum erythropoietin levels in chemotherapy-naive and cisplatin-treated cancer patients.

There are conflicting data about the effects of cisplatin on erythropoietin (EPO) response to anemia. Aim of our study was to investigate whether endogenous EPO response to anemia in cisplatin treated patients was insufficient in comparison to the anemic chemotherapy-naive cancer patients and non cancer patients with iron deficiency anemia. Patients who had hemoglobin (Hb) levels of less than 110 g/l were included in the study. Fifteen chemotherapy- naive cancer patients were enrolled in Group A. Group B consisted of 15 patients who had been treated with three cycles of cisplatin chemotherapy and then became anemic and in Group C were included 15 patients who had iron deficiency anemia, without any malignancy. The mean Hb values were not different between all groups (102.8+/-39.8 g/l, 103.1+/-2.5 g/l and 99.3+/-3.6 g/l in Group A, Group B and Group C, respectively). However, EPO levels were found to be significantly lower in Group A and Group B than Group C (29.63+/-9.09 mU/ml, 20.87+/-2.43 mU/ml and 85.38+/-25.72 mU/ml, respectively; p=0.017 Group A vs. Group C, p=0.005 Group B vs. Group C). No significant difference was found between Group A and B (p=0.917). Opposite the iron deficiency anemia, cancer anemia is associated with an inadequate EPO response to anemia and administration of cisplatin does not lead to it further deterioration.

99mTc-MIBI scintigraphy in untreated stage III multiple myeloma: comparison with X-ray skeletal survey and bone scintigraphy.

Technetium-99m 2-methoxyisobutylisonitrile (99mTc-MIBI) is a lipophilic agent that has been proposed as a useful tracer for the detection of disease sites in patients with multiple myeloma (MM). We performed a prospective study to determine the potential of 99mTc-MIBI imaging for the evaluation of the extent of primary disease in patients with advanced stage MM, compared with skeletal survey and bone scintigraphy. Twenty patients with advanced stage MM at initial diagnosis underwent whole-body 99mTc-MIBI imaging, together with contemporaneous skeletal survey and bone scintigraphy. The findings of 99mTc-MIBI imaging were correlated with the results of skeletal survey and bone scan. All 99mTc-MIBI scans were positive for the presence of active MM, whereas skeletal surveys were positive in 18 patients (90%) with osteolytic lesions. Bone scintigraphy demonstrated MM in only 15 patients (75%). In two patients with no detectable lesions on skeletal survey, 99mTc-MIBI imaging revealed uptake in the spine, corresponding to the abnormalities seen on magnetic resonance imaging (MRI). With respect to the localization of bone lesions, 99mTc-MIBI imaging was superior to bone scintigraphy in 15 patients (75%) and had concordant results with bone scintigraphy in four (20%). 99mTc-MIBI imaging is a very sensitive imaging modality for the identification of the extent of disease in patients with advanced MM. It is clearly superior to bone scintigraphy and complements the results of skeletal survey by finding additional disease sites. Hence, in active MM patients, 99mTc-MIBI imaging has the potential to detect bone marrow disease that cannot be detected by skeletal survey and bone scintigraphy.

The role of triple therapy, age, gender and smoking on the genotoxic effects of Helicobacter pylori infection.

The role of age, gender and smoking on both the genotoxic effects of Helicobacter pylori and the efficacy of eradication therapy in a group of patients with gastritis was investigated. Gastritis was confirmed by endoscopy and biopsy, and the presence of H. pylori by urease testing. Pre- and post-treatment peripheral blood lymphocyte cultures were prepared from 17 patients and 25 metaphases per patients were analysed for sister chromatid exchange (SCE), a well-established technique for the evaluation of human exposure to toxic agents. Treatment with omeprazole, clarithromycin and amoxycillin triple therapy eradicated H. pylori in 94% of patients and significantly reduced the SCE frequency. Pre-treatment SCE frequency was found to be positively correlated with age. Female smokers tended to have higher post-treatment SCE frequencies than male smokers, and pre- and post-treatment SCE frequencies were higher in older males than in older females. Eradication therapy decreased the genotoxicity of H. pylori, but age in males and smoking in females may decrease treatment efficacy.