Field Placement Correction Using MV IGRT. Is Postintervention Imaging Necessary?

PurposeOnline image-guided radiation therapy (IGRT) is used for all radical pelvic patients at Radiation Oncology Queensland. One linear accelerator is equipped with megavoltage electronic portal imaging. Daily imaging on this linear accelerator introduces a dose burden that must be accounted for in the planning process. This dose burden is further complicated by postintervention images taken to verify field placement corrections. Analysis of setup errors and number and management of isocenter shifts was also used to identify an appropriate dose burden to be applied.MethodThe IGRT data of 50 radical pelvic patients were retrospectively collected and analysed, and the number of isocenter moves made was assessed. Statistical analysis of systematic and random errors, both preintervention and postintervention, was undertaken. Inclusive in this analysis was the number of times postintervention images revealed an error in manually entered isocenter shifts. The imaging dose used was also investigated.ResultsOnline IGRT was able to reduce the setup error to <2 mm for all orthogonal planes. Postintervention imaging was shown to be necessary to assess field placement, because manual errors in field placement were found to occur. The generic dose burden in use was found to be excessive.ConclusionDaily IGRT is now considered an essential tool in modern radiation therapy. Postintervention imaging is required to ensure correct isocenter placement on linear accelerators where the process is manual. The current estimate of the worst-case scenario dose burden may be reduced to either incorporate a “population” dose or a more realistic absolute maximum dose. Any removal of a quality assurance process such as this requires evidence, consultation, and careful consideration.     

Individualized EEG source reconstruction of Stroop interference with masked color words

A masked version of the classic color Stroop task was used to study interference effects with stimuli of variable visibility. Pattern masks with different stimulus onset asynchronies (SOAs) reduced the visibility in three steps. We took EEG recordings to measure neural correlates of Stroop interference and their relation to stimulus visibility. The analysis of event-related potentials indicated that N400 differences between congruent and incongruent trials varied with the degree of visibility, leaving no differences with stimuli near identification threshold. An equivalent current dipole model (ECD) was used to map source activity onto regions known to reflect interference-related activity. As expected, the anterior cingulate cortex (ACC) signaled the biggest differences between congruent and incongruent trials. As with event-related potentials, these differences disappeared with reduced stimulus visibility. In addition to equivalent current dipole modeling, Stroop-related neural sources were confirmed by means of current density reconstruction (SWARM) based on individualized boundary element models (BEMs) and a cortical constraint.     

68-Jahre-Altersgrenze: Einstweiliger Rechtschutz geboten

Ohne Zusammenfassung     

Alemtuzumab (Campath-1H) induction therapy and dendritic cells: Impact on peripheral dendritic cell repertoire in renal allograft recipients

Dendritic cells (DC) are the most potent antigen-presenting cells (APC) and are pivotal for initiating allograft immunity. Recently, particular DC subsets have been implicated also in allogeneic T cell hyporesponsiveness. Alemtuzumab (anti-CD52, Campath-1H) is a novel T cell depleting antibody that is currently under investigation for the use in allogeneic organ transplantation. While recent studies demonstrated a conspicuous effect of alemtuzumab on peripheral DC in clinical graft-versus-host disease, its efficiency in patients receiving allogeneic organ transplants is still undefined. In the present study we assessed the peripheral DC repertoire in kidney transplant recipients after either alemtuzumab induction therapy followed by FK506 monotherapy or after conventional immunosuppression (FK506, mycophenolate mofetil and steroids) without any induction agent. Induction with alemtuzumab caused a strong and sustained reduction of the total number of peripheral DC and a significant shift from myeloid to plasmacytoid DC subsets (mDC/pDC ratio) as early as 1 month post-transplantation. These data show that alemtuzumab induction targets the peripheral DC repertoire, which might add another mechanism allowing immunosuppressive drug minimization. Further studies are warranted to further elucidate the functional significance of these finding in the setting of allogeneic organ transplantation.     

Long-term relapse-free survival with supratentorial primitive neuroectodermal tumor in an adult: a case report

Summary Objective In adults, supratentorial primitive neuroectodermal tumor (sPNET) is a very rare undifferentiated embryoblastic neoplasm. Prognosis is worse in comparison to infratentorial medulloblastoma. Older age appears to be prognostically favorable. At present, 5-year survival rates remain below 50% in all age groups. Survival longer than 15 years in an adult has only been reported once so far. Case report In 1987, a 33-year-old-male patient presented with seizures following a six-month’s history of dizziness. CT- and MRI-scans revealed a right occipital tumor with moderate contrast enhancement. The tumor was completely removed. The original histological diagnosis was that of an undifferentiated sarcoma, malignant hemangioendothelioma, grade III. The patient was treated by CyVADIC chemotherapy and conventional radiation therapy (60 Gy). Admission for another reason in 2003 led to a re-evaluation of the original diagnosis. Microscopy revealed a malignant, highly cellular, poorly differentiated tumor with a desmoplastic component. Up to 20% of tumor nuclei were labeled for Ki-67. Almost all cells were stained for neuron specific enolase and NGF-Rp75, with neuronal and glial markers being present to a variable extent. According to these findings, the diagnosis was changed to a sPNET (WHO IV°). Other tumor entities were excluded by immunohistochemistry. Conclusions Although the prognosis of sPNET is reported to be poor, a small fraction with a rather benign biological and clinical behavior exists. Parameters determining long-term-survival in sPNET are not yet known. Whenever possible, complete surgical resection should be attempted followed by postoperative radiotherapy. The value of chemotherapy is an issue of continuous investigation. Supratentorial primitive neuroectodermal tumor is a very rare and highly malignant neoplasm in adults, carrying a poor prognosis. Complete surgical resection followed by radiotherapy proved to be essential for the outcome. We report the case of long-term survival at more than 17 years in an adult patient treated by surgery, postoperative radiation and chemotherapy.     

Thiolated Chitosans: Design and In Vivo Evaluation of a Mucoadhesive Buccal Peptide Drug Delivery System

Purpose Intravenous application of pituitary adenylate cyclase-activating polypeptide (PACAP) has been identified as a promising strategy for the treatment of type 2 diabetes. To generate a more applicable formulation, it was the aim of this study to develop a sustained buccal delivery system for this promising therapeutic peptide. Methods 2-Iminothiolane was covalently bound to chitosan to improve the mucoadhesive and permeation-enhancing properties of chitosan used as drug carrier matrix. The resulting chitosan–4-thiobutylamidine conjugate was homogenized with the enzyme inhibitor and permeation mediator glutathione (gamma-Glu-Cys-Gly), Brij 35, and PACAP (formulation A). The mixture was lyophilized and compressed into flat-faced discs (18 mm in diameter). One formulation was additionally coated on one side with palm wax (formulation B). Tablets consisting of unmodified chitosan and PACAP (formulation C) or of unmodified chitosan, Brij 35, and PACAP (formulation D) served as controls. Bioavailability studies were performed in pigs by buccal administration of these test formulations. Blood samples were analyzed via an ELISA method. Results Formulations A and B led to an absolute bioavailability of 1%, whereas PACAP did not reach the systemic circulation when administered via formulations C and D. Moreover, in the case of formulations A and B, a continuously raised plasma level of the peptide drug being in the therapeutic range could be maintained over the whole period of application (6 h). Formulations A and B were removed by moderate force from the buccal mucosa after 6 h, whereas formulations C and D detached from the mucosa 4 h after application. Conclusion The study reveals this novel mucoadhesive delivery system to be a promising approach for buccal delivery of PACAP.     

Delayed and non-union of the humeral diaphysis--compression plate or internal plate fixator?

In a retrospective study, two groups of patients with delayed or non-union of the humeral diaphysis were compared. In group A, a 4.5-mm low-contact dynamic compression plate (LCDCP) was used for internal fixation and in group B, an internal plate fixator with locked screws was used. In all patients autologous bone grafting was performed. Group A consisted of 14 patients (mean age 38.9 years) and group B consisted of 19 patients (mean age 54.3 years). The mean duration of the delayed or non-union was 9.3 months (range 3-26 months) in group A and 24.8 months (range 3-216 months) in group B. In group A an average of 1.1 (range 0-2) previous operations had been performed, and in group B an average of 1.6 (range 0-4). One primary nerve palsy was diagnosed in group A and six in group B. Although the patients of group B were older, had longer-lasting non-unions, more previous operations and more severe initial injuries, only in group A was there a hardware failure due to osteoporosis which required re-osteosynthesis. All other patients showed bony consolidation without further operations. The LCDCP and the internal plate fixator both showed high consolidation rates, but we feel that the internal plate fixator may be the more reliable implant, especially in patients with poor bone stock.