Feasibility of using interpolated contours of targets and organs at risk in intensity‐modulated radiation therapy treatment planning for advanced‐stage nasopharyngeal carcinoma

To assess the dosimetric effect of using interpolated contours in planning intensity‐modulated radiation therapy (IMRT) for advanced T‐stage nasopharyngeal carcinoma. The present study focused on T3–T4 tumours where the proximity of targets to neurological organs poses a stringent test on the feasibility of such an approach. Contours of targets and organs were delineated on CT images of 2.5‐mm interval and a reference IMRT plan was generated. An investigative (INV) IMRT plan was then generated with the same planning protocol, but based on interpolated contours that replaced deleted contours on alternate slices. The reference and INV plans were compared. Regarding target coverage, all targets in the INV plans met the acceptance criteria except for the PTV in one case. Regarding organs, the mean dose to 1% volume of the brainstem and spinal cord in the INV plans were kept below their dose limits. No significant differences in the mean doses to others organs were found. Satisfactory target coverage and protection of critical organs to a degree similar to full‐scale contouring could be achieved with use of interpolated contours. The saving in manpower time for contouring is expected to significantly improve the throughput of the IMRT planning process.     

Cognitive functions in primary central nervous system lymphoma: literature review and assessment guidelines.

BACKGROUND: Treatment-related neurotoxicity has been recognized as a significant problem in patients with primary central nervous system lymphoma (PCNSL) as effective treatment has increased survival rates. There is, however, a paucity of research on cognitive functions in this population. DESIGN: In a review of the literature, a total of 17 articles that described cognitive outcome in adult PCNSL patients were identified. RESULTS: The studies that assessed cognitive functions after whole-brain radiotherapy combined with chemotherapy reported cognitive impairment in most patients. Patients treated with chemotherapy alone had either stable or improved cognitive performance in most studies. Methodological problems, however, limited the ability to ascertain the specific contribution of disease and various treatment interventions to cognitive outcome. On the basis of the literature review, a battery of cognitive and quality-of-life (QoL) measures to be used in prospective clinical trials was proposed. The battery is composed of five standardized neuropsychological tests, covering four domains sensitive to disease and treatment effects (attention, executive functions, memory, psychomotor speed), and QoL questionnaires, and meets criteria for use in collaborative trials. CONCLUSION: The incorporation of formal and systematic cognitive evaluations in PCNSL studies will improve our understanding of treatment-related neurotoxicity in this population.     

Effects of antiplatelet agents on platelet-induced thrombin generation

OBJECTIVES: The influence of antiplatelet agents on platelet-induced thrombin generation may increase the risk of bleeding. Assessment of the endogenous thrombin potential (ETP), is therefore a parameter deserving attention in early pharmacodynamic studies with antiplatelet drugs. The aim ofthis study was to assess whether an automated ETP-assay can be used to determine possible inhibitory effects of antiplatelet drugs on platelet-associated thrombin generation. METHODS: We first characterized the in vitro dose-response relationship of several platelet agonists (ADP, collagen, U46619, TRAP (amino acid sequence: SFLLRNP) and tissue factor (TF) using the generation of ETP. One submaximal concentration of each agonist was then used to assess the influence of in vivo treatment with aspirin (single oral dose of 500 mg as inhibitor of thromboxane synthesis) and clopidogrel (given orally for 6 days, as an inhibitor of the purinergic P2Y12-receptor on platelets) and in vitro treatment with abciximab (which inhibits the platelet glycoprotein IIb/IIIa-receptor for fibrinogen), on the ETP. RESULTS: The effect of TF and the other platelet inducers on thrombin generation was dose-dependent. Repeat measurements on samples from the same subject, with the same inducer concentration on 2 different occasions showed a variability of approx. 22% (absolute difference between 2 measurements as % of mean). The coefficient on variation of repeat measurements of one sample varied between 7% and 17%, depending on the inducer. After a single dose of aspirin, ETP was reduced by 25-40%, depending on the platelet activating agent used. The reduction in ETP with abciximab in vitro was more pronounced. In contrast, TF-induced ETP was not influenced by aspirin or abciximab. Clopidogrel, administered for 6 days, reduced the ETP by 60% when platelets were stimulated using 20 microM ADP, whereas collagen-induced ETP and TF-induced ETP remained unchanged. CONCLUSIONS: The ETP-method is a sensitive and reproducible method for the detection of drug effects on platelet-induced thrombin generation of high throughput, and can be recommended for studies on the pharmacodynamic profile of drugs interfering with platelet function.     

Effects of the NHE-1 inhibitor cariporide alone or together with the P2Y12 antagonist AR-C 69331 MX on CD62p expression and formation of platelet-leukocyte aggregates

The sodium-hydrogen exchanger isoform 1 (NHE-1) contributes to platelet activation at elevated pH. Effects of NHE-1 inhibitors on platelet degranulation and formation of proinflammatory and procoagulatory platelet-leukocyte aggregates (PLA) and possible interactions with P2Y(12) inhibitors--which also affect platelet degranulation--have not been investigated. Whole blood from healthy human subjects was incubated with the NHE-1 inhibitor cariporide and the P2Y(12) inhibitor AR-C 69331 MX at clinically reasonable concentrations, in the presence of normal pH or in a propionate model to activate the NHE-1 (approximately pH 7.0). The degranulation marker CD62p, the expression of the activated GPIIb/IIIa receptor (PAC-1), and formation of platelet-leukocyte (monocyte) aggregates (PLA) was assessed by flow cytometry. Cariporide at concentrations up to 20 microg/ml had no effects on ADP- (5 microM) or TRAP- (2 microM) induced CD62p expression or PLA formation at normal pH. At pH 7.0 and stimulation with ADP, PLA decreased from 64+/-24% (control) to 47+/-23% under cariporide at 2 microg/ml (p<0.05), and the MFI of PLA (i.e. the platelet mass attached at monocytes) decreased from 547+/-203 to 360+/-96 units (p<0.05). PAC-1 MFI decreased from 66+/-23 to 34+/-18 units (p<0.05) after ADP and from 74+/-29 to 42+/-17 units (p<0.05) after TRAP, respectively. AR-C 69331 MX (10 nM) had inhibitory effects on all parameters irrespectively of the pH, and the combination of both agents at pH 7.0 shows additive effects. In conclusion, our investigation points to-perhaps clinically relevant-effects of NHE-1 inhibition on the degranulation of platelets and formation of platelet-leukocyte aggregates.     

Maligne entarteter perianaler Buschke-Löwenstein-Tumor Ausgedehnte abdominoperineale Rektumamputation und Rekonstruktion mit transpelvinem myokutanem M.-rectus-abdominis-Lappen

Introduction. The Buschke Löwenstein tumor (giant condyloma) in its perianal variant is an extremely rare disease caused by human papilloma virus. Although of histologically benign appearance, it infiltrates and destroys the surrounding tissue. There is a high risk of local recurrence and malignant transformation. The treatment of choice is wide surgical resection. Case. A 56-year-old woman presented with perianal giant condyloma infiltrating the rectum and vagina. The extensive soft tissue defect resulting from wide resection was filled with a transpelvic myocutaneous rectus abdominis flap. Histology showed a squamous cell carcinoma arising in the Buschke Löwenstein tumor with clear resection margins. Therefore, the patient was irradiated locally after uneventful primary wound healing. Conclusion. A simultaneous reconstruction of a large pelvinoperineal soft tissue defect with the transpelvic myocutaneous rectus abdominis flap allows primary healing, accelerated rehabilitation, and safe adjuvant radiotherapy without risk of serious radiation damage to the small bowel by preventing it from protruding into the pelvic defect.     

Dry coating in a rotary fluid bed.

A highly efficient dry coating process was developed to obtain an enteric film avoiding completely the use of organic solvents and water. Using hydroxypropyl methylcellulose acetate succinate (HPMCAS) an enteric coat should be obtained without adding talc as anti-tacking agent because of problems arising from microbiological contamination. Further on, a method was developed preparing isolated films in order to determine the glass transition temperature (T(g)) and the required process temperature. The process was conducted in the rotary fluid bed with a gravimetric powder feeder achieving an exact dosage in contrast to volumetric powder feeder. A three way nozzle was aligned tangential to the pellet bed movement feeding simultaneously powder and plasticizer into the rotary fluid bed. The determined coating efficiency of the talc-free formulation was high with 94% and storage stability regarding tacking could be achieved using colloidal silicium dioxide as top powder. The T(g) of the enteric coat could be determined analyzing the T(g) of isolated films obtained by coating celluloid spheres instead of pellets using the dry coating process in rotary fluid bed. The dry coating process has been demonstrated to be a serious alternative to conventional solvent or water based coating processes.