Abstract Vaccines targeting tumour angiogenesis were recently shown to inhibit tumour growth in animal models. However, there is still a lack of information about the clinical utility of ...anti-angiogenic vaccination. Therefore, here, we aimed to test the clinical effects of a vaccine using glutaraldehyde-fixed human umbilical vein endothelial cells (HUVECs). Six patients with recurrent malignant brain tumours and three patients with metastatic colorectal cancer received intradermal injections of 5 × 107 HUVECs/dose (in total 230 vaccinations). ELISA and flow cytometry revealed immunoglobulin response against HUVECs’ membrane antigens. ELISPOT and chromium-release cytotoxicity assay revealed a specific cellular immune response against HUVECs, which were lysed in an effectors:targets ratio-dependent manner. Gadolinium-contrasted MRI showed partial or complete tumour responses in three malignant brain tumour patients. Except for a DTH-like skin reaction at the injection site, no adverse effect of vaccination could be observed. Our results suggest that the endothelial vaccine can overcome peripheral tolerance of self-angiogenic antigens in clinical settings, and therefore should be useful for adjuvant immunotherapy of cancer.
Aim: To provide a profile of second malignant neoplasms (SMN) in patients with childhood primary malignant brain tumour originating from neuroepithelial tissues with latest data in a ...population‐based study.
Methods: Surveillance, Epidemiology, and End Results (SEER) database (1973–2007) was used to identify above‐stated patients. SMN patients were further identified, and standardised incidence ratios (SIRs) and excess absolute risks (EARs) for risk‐factor‐decided subgroups were calculated. Univariate and multivariate analyses of the association between cumulative incidence of SMN and the risk factors were performed in the whole population.
Results: A total of 106 patients were identified as having SMNs. EARs peaked at age at primary diagnosis of 10–14. Males had higher SIRs and EARs than females. Both SIRs and EARs increased after 1990. Age was statistically significant in both univariable and multivariable analyses for cumulative incidence of SMN and RT was not significant in both the analyses, in the whole population of 9075 patients. After follow‐up recalculation, matched patients in the ≥1990 group had slightly shorter median interval between primary and secondary cancer than those in the <1990 group, but with no significance.
Conclusion: The risk of SMN in children with primary malignant brain tumours in a more advanced treatment era might have changed. During making further advances in the treatment of these neoplasms, minimising toxicities while maintaining promising prognostic outcomes will keep being our goal.
To investigate the symptom experience, access to supportive care services and rehabilitation of patients with a primary malignant brain tumour (PMBT) and their carers.
A case review of 70 patients ...with a diagnosis of PMBT who received palliative care in five specialist palliative care units between July 2005 and June 2006. The review examined patients' symptom experience, care issues, access to rehabilitation and access to supportive care services.
The two most significant issues experienced by patients and identified in the case review were hemiparesis (17%) and cognitive problems (16%). There were a number of care problems concerning safety related to mobility and falls (9%). Symptoms related to fatigue and tiredness were reported infrequently. There was an absence of information relating to the needs of informal carers; however, 18% of carers accessed bereavement counselling services following the death of the person they cared for.
The needs of carers were not found to be routinely documented within the case notes. For some patients, referral to specialist palliative care services occur late in the illness trajectory, which means that patients and carers may not be able to access the full range of supportive care services available. Initial assessment of patients should identify the range of support services that both carers and patients are offered; and the uptake and response to services should be documented throughout the illness trajectory.
OBJECTIVES to evaluate quality of life in patients with malignant brain tumour with stable disease after combined treatments in comparison to patients with other chronic neurological conditions, and ...to explore the relation of quality of life to clinical, pathological, affective and cognitive factors. METHODS fifty seven patients who were stable after surgery, radiotherapy and chemotherapy and 24 controls with spastic paraparesis, peripheral neuropathies, myasthenia, ataxia, Parkinson’s disease, or multiple sclerosis, were studied. Patients were evaluated by functional living index-cancer, Karnofsky performance status, activity of daily living, self-rating depression scale, state-trait anxiety inventory, and tests for cognitive abilities. RESULTS separate Mann-Whitney test comparisons did not show any difference in measures of health related quality of life (functional living index-cancer), autonomy in daily life (activity of daily living), or mood between tumour and control patients, although the first had slower mental speed and worse attention. Seventy three per cent of patients with brain tumour and 58% of the control patients continued or resumed previous work activity. Quality of life was significantly associated with depression, state anxiety, and performance status in the patients with brain tumour, whereas in control patients, state anxiety was the only factor related to quality of life. CONCLUSIONS after intensive multimodality treatments, selected patients with brain tumour with stable disease may have satisfactory quality of life that may be not worse than in patients with other chronic neurological illnesses. During the period of stable disease, depressed mood, possibly a reaction to impaired physical and cognitive performance, seems to play a major role in determining quality of life.
Photodynamic techniques such as photodynamic diagnosis (PDD), fluorescence-guided tumour resection (FGR) and photodynamic therapy (PDT) are currently undergoing intensive clinical investigations as ...adjuvant treatment for malignant brain tumours. The following chapter provides an overview on the current clinical data and trials of PDT as well as photosensitizers, technical developments and indications for photodynamic application in neurosurgery. Besides many clinical phase I/II trials for PDT for malignant brain tumours, there are only few controlled clinical trials following tumour resection. Variations in treatment protocols, variation of photosensitizers and light dose make the evaluation scientifically difficult; however there is a clear trend towards prolonging median survival after one single photodynamic treatment as compared to standard therapeutic regimens. According to the meta analysis the median survival after PDT for primary glioblastoma multiforme (WHO grade IV) was 22 months and for recurrent GBM was 9 months as compared to standard conventional treatment, in which it is 15 and 3 months, respectively. Fluorescence-guided resection of the tumour demonstrated significant greater reduction of tumour burden. The combination of PDD/ FGR and intraoperative PDT ("to see and to treat") offers an exciting approach to the treatment of malignant brain tumours. PDT was generally well tolerated and side effects consisted of occasionally increased intracranial pressure and prolonged skin sensitivity against direct sunlight.
Summary Objective This study investigated whether or not the effect of contrast medium on diffusion tensor magnetic resonance imaging (DTI) is time-related in patients with malignant brain tumours. ...Patients and methods Twelve patients who only had malignant brain tumours were included in the study. DTI acquisitions were performed five times consecutively: twice before, once during, then twice after contrast injection. Diffusion indices were mapped and regions of interest (ROIs) were placed in the tumour, peritumoral edema and contralateral normal brain tissue. Repeated-measures ANOVA was used to investigate the effects of time on contrast medium in relation to diffusion indices. Results Precontrast DTI was redefined as “pre” by averaging the two before-contrast scans, as there were no statistically significant differences between them. There were statistically significant differences at four time points for only the edema ROI for fractional anisotropy and the first-largest eigenvalue, but not for trace and the second-largest eigenvalue. Conclusion The effects of contrast medium on DTI were time-dependent for diffusion anisotropic indices. DTI obtained at > 6 min after contrast injection does not cause significant changes in diffusion isotropic and anisotropic values.
Non-neoplastic demyelinating processes of the brain with ring enhancing lesions and mass effect on MRI imaging, mimicking malignant brain tumours, are rare phenomena.
We document the case of a 32 ...year old male with clinical, radiological and initial histological findings, suggestive of a malignant brain tumour. Additional investigations confirmed the diagnosis of multiple sclerosis.
This case is significant as the lesion could not be easily distinguished from a malignant brain tumour on imaging alone. Cases such as this illustrate the importance of considering a demyelinating process in the differential diagnosis of tumour-like brain lesions.
Aims: To investigate the participation of DMBT‐1, a candidate tumour suppressor gene, in the development of intrahepatic cholangiocarcinoma via intraductal papillary neoplasm of the liver (IPN‐L) ...arising in hepatolithiasis. DMBT‐1 plays a role in mucosal immune defence.
Methods and results: The expression of DMBT‐1 was examined immunohistochemically in biliary epithelial cells in hepatolithiasis (n = 25), invasive and non‐invasive cholangiocarcinoma associated with hepatolithiasis (n = 52), IPN‐L with hepatolithiasis (n = 49), cholangiocarcinoma without hepatolithiasis (n = 32), and 10 normal control livers. DMBT‐1 was expressed more frequently in the biliary epithelia of hepatolithiasis when compared with normal livers (P < 0.05). DMBT‐1 expression was also frequent in IPN‐L (57%) and non‐invasive cholangiocarcinoma (79%). By contrast, DMBT‐1 was decreased in invasive cholangiocarcinoma with and without hepatolithiasis (50% and 30%, respectively) (P < 0.05). The homozygous deletion of the DMBT‐1 gene was recognized in four (20%) of 20 cholangiocarcinoma tissues and two (50%) of four cholangiocarcinoma cell lines, corresponding to the reduction of DMBT‐1 expression. No deletion was detected in hepatolithiasis tissues.
Conclusion: DMBT‐1 expression is increased in IPN‐L and non‐invasive cholangiocarcinoma as well as in biliary epithelia in hepatolithiasis. Decreased expression of DMBT‐1 and homozygous deletion of the DMBT‐1 gene in invasive cholangiocarcinoma suggest that they occur in the late stage of cholangiocarcinogenesis.
SRT is a high-precision technique of radiotherapy which delivers focused irradiation to small target volumes. In the context of external beam radiotherapy it can be described as stereotactically ...guided conformal radiotherapy. As the technique originated from neurosurgical technology, it has initially been limited to single fraction treatment. However, with the use of relocatable fixation devices the way ahead particularly in its application in the treatment of brain tumours is in fractionated SRT. Currently, single fraction SRT/radiosurgery is of proven value only in the treatment of small inoperable arteriovenous malformations. It is being exploited in the management of brain tumours but so far remains as experimental treatment. We have demonstrated that fractionated SRT in patients with gliomas is a non-invasive equivalent to brachytherapy and in patients with solitary metastases a non-invasive alternative to surgical excision. However, the treatment is not without side effects, and the long-term effectiveness and toxicity of SRT, particularly with the use of unconventional fractionation, is not defined. The future use of SRT in the treatment of brain tumours should not be guided simply by the technical possibilities but by a rational appraisal of all treatment options to achieve the best disease control, survival and toxicity. Although there is potential for benefit in a number of small tumours, SRT cannot at present be recommended as the primary treatment in any tumour. In addition, its use should be discouraged in the treatment of unbiopsied brain lesions and as the major form of treatment of pineal germinomas. The technology of stereotactic radiotherapy is evolving, and it is likely that SRT will be integrated into conventional radiotherapy practice to become simply a high-precision technique of radiotherapy delivery in everyday use.
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