10 years survival of patient with lung cancer and cerebral metastasis

The authors describe the case of survival for the period of 10 years after brain metastasis surgery and removal of the left lung upper lobe due to adeno-squamous cells carcinoma. Surgery did not generate any complications. Within 8 years after the surgery the radiological examination showed infiltrations resembling changes typical for tuberculosis. Microbiological analysis showed a culture of Mycobacterium kansasi leading to diagnosis of mycobacteriosis. Hence the antituberculous treatment was extended to 12 months to be interrupted due to liver damage. Two years later the patient experienced incident of haemoptysis. Detailed examination and assessment of the respiratory tract condition revealed COPD without features of renewal of the neoplastic process or infection by Mycobacterium tuberculosis or mycobacterium other than tuberculosis. This case demonstrates that aggressive surgical approaches to lung cancer with solitary cerebral metastasis significantly improve patient survival and justifies its widespread use.     

Disturbed function of the blood–cerebrospinal fluid barrier aggravates neuro-inflammation

Multiple sclerosis (MS) is a chronic neuro-inflammatory disorder, which is marked by the invasion of the central nervous system by monocyte-derived macrophages and autoreactive T cells across the brain vasculature. Data from experimental animal models recently implied that the passage of leukocytes across the brain vasculature is preceded by their traversal across the blood–cerebrospinal fluid barrier (BCSFB) of the choroid plexus. The correlation between the presence of leukocytes in the CSF of patients suffering from MS and the number of inflammatory lesions as detected by magnetic resonance imaging suggests that inflammation at the choroid plexus contributes to the disease, although in a yet unknown fashion. We here provide first insights into the involvement of the choroid plexus in the onset and severity of the disease and in particular address the role of the tight junction protein claudin-3 (CLDN3) in this process. Detailed analysis of human post-mortem brain tissue revealed a selective loss of CLDN3 at the choroid plexus in MS patients compared to control tissues. Importantly, mice that lack CLDN3 have an impaired BCSFB and experience a more rapid onset and exacerbated clinical signs of experimental autoimmune encephalomyelitis, which coincides with enhanced levels of infiltrated leukocytes in their CSF. Together, this study highlights a profound role for the choroid plexus in the pathogenesis of multiple sclerosis, and implies that CLDN3 may be regarded as a crucial and novel determinant of BCSFB integrity.     

Deletion of claudin-10 (Cldn10) in the thick ascending limb impairs paracellular sodium permeability and leads to hypermagnesemia and nephrocalcinosis

In the kidney, tight junction proteins contribute to segment specific selectivity and permeability of paracellular ion transport. In the thick ascending limb (TAL) of Henle's loop, chloride is reabsorbed transcellularly, whereas sodium reabsorption takes transcellular and paracellular routes. TAL salt transport maintains the concentrating ability of the kidney and generates a transepithelial voltage that drives the reabsorption of calcium and magnesium. Thus, functionality of TAL ion transport depends strongly on the properties of the paracellular pathway. To elucidate the role of the tight junction protein claudin-10 in TAL function, we generated mice with a deletion of Cldn10 in this segment. We show that claudin-10 determines paracellular sodium permeability, and that its loss leads to hypermagnesemia and nephrocalcinosis. In isolated perfused TAL tubules of claudin-10-deficient mice, paracellular permeability of sodium is decreased, and the relative permeability of calcium and magnesium is increased. Moreover, furosemide-inhibitable transepithelial voltage is increased, leading to a shift from paracellular sodium transport to paracellular hyperabsorption of calcium and magnesium. These data identify claudin-10 as a key factor in control of cation selectivity and transport in the TAL, and deficiency in this pathway as a cause of nephrocalcinosis.     

Visual disorders,the prosopometamorphopsia and prosopagnosia type in the early days after the onset of brain hemorrhagic stroke – a case report

Presented case report illustrates symptoms of prosopometamorphopsia (PM) and prosopagnosia, observed in the early days after the onset of a hemorrhagic stroke resulting from a complication of endovascular treatment of intracranial aneurysms and the use of anticoagulation therapy. PM is a visual disorder in which faces are perceived as distorted. The female patient described in the present study reported that faces she looked at seemed younger or older than in reality or as if they were dirty, swollen, or with a grimace. She also experienced symptoms of prosopagnosia, which is difficulty of recognizing familiar faces of people (e.g., of her husband and daughter). In the interview 6 months after the first examination, the patient reported spontaneous withdrawal of the visual disturbances.     

Efficacy of concomitant and adjuvant temozolomide in glioblastoma treatment. A multicentre randomized study

Background and purposeThe common treatment in patients with newly diagnosed glioblastoma multiforme is the ultimately radical surgical removal of the tumour combined with radiotherapy. This study compared safety and efficacy of radiotherapy alone with radiotherapy combined with temozolomide (TMZ) given before, during, and after radiotherapy.Material and methodsThe patients operated on for glioblastoma multiforme during the first 21 postoperative days were randomly assigned to the group treated with radiotherapy alone (involved-field radiotherapy in 2 Gy fractions daily five times a week up to the total of 60 Gy over 6 weeks of treatment) or to the group treated with radiotherapy and TMZ, initially in the dose of 200 mg/m² during 5 postoperative days and after 23 days followed by 75 mg/m² of body surface area daily, 7 days a week (from the first to the last day of radiotherapy). On completion of radiotherapy, five complementary courses of TMZ were introduced (150–200 mg/m² for 5 days, repeated every 28 days). The primary outcome measure was overall survival.ResultsFifty-eight patients from 3 centres were included in the study. The mean age of patients was 55 years and all the patients underwent a surgical procedure of glioblastoma removal. The mean overall survival in the group treated with TMZ was 16.0 months, whereas in the group with radiotherapy alone the overall survival reached 12.5 months. 24-month survival reached 23% in patients treated with TMZ and 6.7% in those who received radiotherapy only. Haematological complications of third or fourth degree were present in 10% of patients treated with radiotherapy and TMZ.ConclusionsThe introduction of TMZ before, during and after radiotherapy for newly diagnosed glioblastoma multiforme gives clinically and statistically significant improvement of survival with unremarkably increased toxicity of the treatment.     

Cost–utility and cost-effectiveness of physical exercise during adjuvant chemotherapy

Introduction

A home-based, low-intensity physical activity program (Onco-Move) and a supervised, moderate-to-high intensity, combined resistance and aerobic exercise program (OnTrack) have proven to be effective in maintaining physical fitness and reducing fatigue among breast cancer patients undergoing adjuvant chemotherapy. This study evaluated the cost–utility and cost-effectiveness of Onco-Move and OnTrack.

Methods

A total of 230 patients were randomized to Onco-Move, OnTrack, or usual care (UC). Health outcomes included quality-adjusted life years (QALYs), general and physical fatigue, and physical fitness measured at baseline, end of chemotherapy, and 6-month follow-up. Societal costs included professional and informal health care, work absenteeism, and unpaid productivity costs. Cost data were based on 3-monthly questionnaires, supplemented by medication data obtained from pharmacies.

Results

Onco-Move is not likely to be cost-effective due to the relatively high willingness-to-pay necessary to reach reasonable probabilities of cost-effectiveness (QALY, general and physical fatigue). Incremental cost-effectiveness ratios for OnTrack compared to UC were €26,916/QALY, €788/1-point decrease in general fatigue and €1402/1-point decrease in physical fatigue. The probability of OnTrack being cost-effective ranged from 31% at a willingness-to-pay (WTP) of €0–79% at a WTP of €80,000/QALY, 97% at a WTP of €15,000/1-point decrease in general fatigue, and 86% at a WTP of €24,000/1-point decrease in physical fatigue. Both interventions had a low probability of being cost-effective for physical fitness. The probability of cost-effectiveness for both interventions was greater among compliant participants.

Conclusions

Onco-Move is not likely to be cost-effective. Depending on the decision-makers’ willingness-to-pay, OnTrack could be considered cost-effective in comparison with UC. Trial registration Clinical trial registration number of the Netherlands Trial Register—NTR2159.

     

Surgical treatment of intraventricular ependymomas and subependymomas

Background and purposeThe aim of the study was to present our experience in the surgical treatment of intraventricular ependymomas and subependymomas with special consideration to the evaluation of the surgical outcome and risk of tumour recurrence.Material and methodsWe report a series of 36 consecutive patients treated surgically for intraventricular ependymoma or subependymoma in the years 1992–2008. There were 26 lateral ventricle and 10 fourth ventricle tumours. Complete resection was achieved in 19 patients while the remaining 17 patients underwent either subtotal or partial resection. Histopathological evaluation revealed ependymoma, subependymoma and anaplastic ependymoma in 20, 11 and 5 cases, respectivelyResultsEight patients died after surgery due to postoperative brain injury. Five patients were severely disabled postoperatively: one patient developed hemiparesis, three patients presented adynamic syndrome, and one patient developed severe cerebellar ataxia subsequent to vermis injury. All patients with posterior fossa tumours presented with lower cranial nerve deficit. Seventeen patients received radiotherapy postoperatively. There were five recurrent tumours during follow-up; three patients underwent subsequent reoperation. Importantly, five patients with supratentorial tumours and a history of incomplete resection with postoperative radiotherapy had no tumour recurrence in over 10 years’ follow-up.ConclusionsIntraventricular ependymomas and subependymomas still remain a surgical challenge due to a relatively high incidence of incomplete tumour resections and/or permanent neurological complications associated with their removal. Still, even incomplete tumour removal with subsequent radiotherapy facilitates long-term progression-free survival in some cases.