Distress in patients with newly diagnosed brain tumours.

OBJECTIVE: Patients with intracranial tumours often suffer from clinically relevant psychological distress. However, levels of distress and contributing factors have not been systematically evaluated for the early course of the disease. Using the National Comprehensive Cancer Network's Distress Thermometer (DT), we evaluated the extent and sources of distress within a population of patients with intracranial neoplasms. METHODS: One hundred and fifty-nine patients were included who underwent craniotomy for newly diagnosed intracranial tumours at our department. All patients completed the DT questionnaire, a single-item 11-point visual analogue scale measuring psychological distress. The appendant problem list (PL) consists of 40 items representing problems commonly experienced by cancer patients. Patients were asked to mark any experienced sources of distress. RESULTS: Percentage of patients suffering from relevant distress was 48.4% (cut-off ≥6). DT-scores were significantly associated with depression and anxiety as well as reported number of concerns. On average, patients reported 6.9 sources of cancer-related distress. Objective medical data (e.g. tumour stage) as well as sociodemographic data (e.g. gender, IQ) were not associated with psychological distress at this early phase. CONCLUSIONS: Prevalence of elevated distress is high shortly after primary neurosurgical treatment in patients with intracranial tumours and cannot be predicted by objective data. As a consequence, sources of distress can and should be routinely assessed and targeted in these individuals in this particular period. Further studies are needed to help to identify patients who are at risk of suffering from long-term emotional distress in order to enable targeted psychosocial intervention.

Surgical treatment for brain metastases: Prognostic factors and survival in 309 patients with regard to patient age.

Brain metastases are the most common intracranial tumors. Overall, the only accepted prognostic factors are patient age and performance status. However, several other factors are considered before surgery. We performed a retrospective analysis of 309 patients who underwent surgical resection of newly diagnosed brain metastases between 1994 and 2004. Univariate survival analysis revealed age, performance status, extracranial metastases, complete resection, radiotherapy and re-craniotomy as prognostic indicators. Multivariate analysis determined that patient age, performance status, extracranial metastases, radiotherapy and re-craniotomy are independent factors of prolonged survival. We statistically estimated the age threshold separating patients with favorable outcomes from those with unfavorable prognoses. Using the Kaplan-Meier analysis this threshold can be set at 65 years. Multivariate analysis of patients >65 years revealed the presence of co-morbidities, the number of brain metastases, post-operative performance status and radiotherapy as independent prognostic factors.

Outcome evaluation in glioblastoma patients using different ranking scores: KPS, GOS, mRS and MRC.

Patient performance is an overall accepted independent prognostic factor in glioblastoma patients. Its estimation is essential for treatment planning, follow-up and clinical trials. Patient performance is mostly determined by usage of the Karnofsky Performance Score (KPS) for cancer patients. However, several other ranking scores have been developed specifically for patients with neurological diseases: Glasgow Outcome Score (GOS) for trauma patients, modified Ranking Score for stroke patients and Medical Research Council brain prognostic index (MRC) for brain tumour patients. The aims of this study were: (1) to compare these four performance scores in their ability to determine patient survival; and (2) to compare the prognostic value of performance with that of other prognostic factors. Univariate and multivariate survival analysis was used. Survival analysis revealed a high correlation to survival for all four scores. The maximum derivation of the curves was shown for the MRC and GOS. Performance had more clinical impact in determining patient survival than age and tumour resection. Differential treatment planning may need the formation of more than two patient groups. This was possible with the MRC, as well as the GOS and KPS. Forming more than three patient groups was not effective with any score.

Endoglin expression in metastatic breast cancer cells enhances their invasive phenotype.

Endoglin is a cell-surface adhesion protein as well as a coreceptor for transforming growth factor-beta (TGF-beta). It is located on endothelial and few other cells, but also found on certain tumor cells. Brain metastatic breast tumor cells derived from the MDA-MB-231 cell line heavily express endoglin in contrast to the corresponding parental ones. To clarify whether this determines their invasive phenotype, we compared their biological properties with endoglin-silenced brain-metastatic cells, low-expressing parental cells and these transfected with L- and S-endoglins, isoforms transducing or lacking TGF-beta signals. All L-endoglin-overexpressing cells were characterized by numerous invadopodia where endoglin was preferentially localized. Endoglin-expression resulted in elevated levels of the matrix metalloproteinases (MMP-1 and MMP-19) and downregulation of the plasminogen activator inhibitor-1. In Boyden-chamber and wound-healing assays, endoglin-overexpressing cells showed a considerably higher migration and chemotaxis to TGF-beta. In 3D spheroid confrontation assays between breast tumor cells and TGF-beta-secreting glioma cells, high L-endoglin-expressing cells invaded into the glioma-spheroids whereas low-endoglin-expressing cells dissociated in the culture; invasion was blocked by TGF-beta antibodies. In contrast to parental cells, endoglin-overexpressing cells invaded deeply into mouse brain slices. Thus, endoglin expression on tumor cells enhances their invasive character by formation of invadopodia, extracellular proteolysis, chemotaxis and migration.

Primary peripheral T-cell lymphoma of the central nervous system.

UNLABELLED: A 47-year-old man was admitted to our hospital with a nine-week history of visual disturbance, headache, disorientation and facial nerve palsy. Serial cranial magnetic resonance imaging (MRI) revealed progressive bilateral occipital edema with hemorrhage and meningeal involvement. There were no hints of hereditary or acquired immunodeficiency. Laboratory examination for bacterial and viral causes was negative. Open brain biopsy revealed primary central nervous system lymphoma of the extraordinary rare so-called "peripheral" T-cell type. The further course was fatal; the patient died 10 weeks after the onset of symptoms from tumor progression before planned chemotherapy could be started. CONCLUSION: If primary central nervous system lymphoma (PCNSL) is suspected, brain biopsy -- either open biopsy or stereotactic biopsy -- should be performed straight away to enable a rapid start of chemotherapy and/or radiotherapy. Peripheral T-cell lymphoma was highly aggressive in this case leading to the patient's death within several weeks.

p53, mdm2, EGFR, and msh2 expression in paired initial and recurrent glioblastoma multiforme.

BACKGROUND: The clinical course of glioblastoma multiforme is characterised by invasive growth and regular recurrence. Many genetic alteration have been identified in the genesis of the disease. However, information about immunohistochemical expression in recurrent lesions is sparse. OBJECTIVES: To determine (1) whether the p53/mdm2/EGFR/msh2 expression pattern differs in initial v recurrent glioblastoma multiforme; (2) whether a possible change in expression correlates with prognostic variables (progression-free survival time, total survival time); and (3) whether chemotherapy in addition to surgery and radiotherapy influences the p53/mdm2/EGFR/msh2 expression profile. METHODS: 27 patients were studied. They met the following criteria: histologically confirmed diagnosis of glioblastoma multiforme (WHO IV); total tumour resection at initial craniotomy; at least one re-craniotomy for glioblastoma multiforme recurrence; age 21 years or older. All underwent radiotherapy of at least 54 Gy, and 17 received additional chemotherapy. Immunohistochemical staining of initial tumours and recurrences was done with the following monoclonal antibodies: anti-p53 (DO-1), anti-mdm2 (IF-2), anti-EGFR (H11), and anti-msh2 (AB-1). RESULTS: In comparison with the initial tumour, recurrent lesions were characterised by reduced expression of p53 (p < 0.0001) and msh2 (p = 0.0012), while the numbers of mdm2 (p = 0.02), EGFR (p < 0.0001), and msh2 positive specimens (p < 0.0001) were reduced. Chemotherapy was associated with reduced msh2 expression (p < 0.0001). Immunohistochemical variables were not associated with patient survival. CONCLUSIONS: There are significant differences in the p53/mdm2/EGFR/msh2 expression patterns in initial v recurrent glioblastoma multiforme. There may be interactions between chemotherapy and changes in the msh2 expression.

Age-related expression of p53, Mdm2, EGFR and Msh2 in glioblastoma multiforme.

OBJECTIVE: Glioblastoma multiforme (GBM) is a major cause of morbidity and mortality in neurosurgical patients. Despite the overall poor prognosis a range in survival times exists. Many approaches have been undertaken to define patient subgroups based on molecular changes. The aim of this study was to assess a possible correlation between the immunohistochemical p53, Mdm2, EGFR and Msh2 expression and age. METHOD: 143 patients (77 male, 66 female) were included in this retrospective study who underwent craniotomy for newly-diagnosed GBM between May 1994 and February 2000. For statistical analysis, patients were separated into three age groups: 1. < 40 years, 2. 40-60 years, 3. > 60 years. Immunohistochemical staining (IHC) was performed using anti-p53 (clone DO-1), anti-Mdm2 (clone IF-2), anti-EGFR (clone H11) and anti-Msh2 antibodies (clone AB-1). The results were compared with the Ki67/MIB-1 proliferation index (Ki67 PI) and patient survival. FINDINGS: P53 protein expression was significantly decreasing with advanced age (p < 0.05) whereas EGFR and Mdm2 expression was increasing (p < 0.05; p=0.01). Msh2 expression was unrelated to age. Multivariate analysis revealed Msh2 protein expression as a significant predictor of prolonged survival (p=0.004) whereas p53, Mdm2 and EGFR were not associated with patient survival. P53, Mdm2, EGFR and Msh2 expression was not associated with the Ki67 PI. INTERPRETATION: Our results support the hypothesis that in GBM patients a complex relationship exists between the p53, Mdm2 and EGFR expression and age. Msh2 expression is not related to age. Notably, nuclear Msh2 expression turned out to be an independent prognostic indicator.

Therapeutical considerations in patients with intracranial venous angiomas.

The clinical presentation of intracranial venous angiomas are usually headache, seizures or dizziness. Very often these anomalies are found incidentally on magnetic resonance imaging (MRI). We reviewed 35 patients, which were examined in our department between 1994 and 2000. Only one patient became symptomatic with an intracranial haematoma, which was removed surgically. In three patients an associated cavernous angioma was found, which was removed successfully with preservation of the coexisting venous angioma. There is no indication in operating a venous angioma because the risk of postoperative deterioration caused by venous infarction is high. When removing cavernous angiomas the associated venous angioma has to be preserved.

Cytotoxicity of 2-aldo- and 2-ketopyridine-N(4)-substituted thiosemicarbazones and mode of action in human Tmolt4 cells.

The 2-aldo- and 2-ketopyridine-N(4)-substituted thiosemicarbazones and their copper complexes demonstrated potent cytotoxic activity against a series of murine and human suspended cultured tumor cells. Selected compounds were active against the growth of cultured cells from solid human tumors, i.e. Mck-7 breast effusion, lung A549 and lung MB-9812, bone SOS-2 and clear cell Caki renal tumor. In Tmolt4 T cell leukemia cells the compounds inhibited the syntheses of DNA, RNA and protein over 60 min at 25 to 100 microM. Multiple target sites in nucleic acid metabolism were suppressed by the agents, i.e. DNA polymerase alpha, ribonucleoside reductase, dihydrofolate reductase, de novo purine synthesis, thymidylate synthetase and nucleoside kinases. The total effects of the agents on DNA metabolism led to the reduction of deoxyribonucleotide pools as well as DNA fragmentation.

Malignant peripheral nerve sheath tumours--report of 8 cases and review of the literature.

BACKGROUND: Though Malignant peripheral nerve sheath tumours (MPNST) are a rare entity accounting for 5-10% of soft-tissue sarcomas they are an important differential diagnosis to benign tumours of the peripheral nervous system regarding treatment and prognosis. METHOD: We present our experience with eight patients who underwent surgery for MPNST at the Department of Neurosurgery between 10/1990 and 9/1999. The median age was 37 years [range: 13-64], the male/female ratio was 1:1. Two patients suffered from Neurofibromatosis type 1. Paraffin embedded tumour specimens were immunohistochemically stained for S-100, p53 and Ki67/MIB-1. FINDINGS: The most frequent initial symptoms were local swelling and pain followed by irritation of cranial nerves and spinal ataxia. Four tumours were localised at the head & neck region, three were found in the extremities and one tumour was located on the trunk. All patients underwent surgery with curative intent, but total resection, defined by negative surgical margins, was achieved in only 3 cases. All of these developed local recurrence with a mean disease free survival time of 10.6 months. In five cases, adjuvant radiation was given. During follow up, three patients developed distant metastases located in the lung, liver and subcutaneous tissue. Five out of eight patients died during follow-up with a mean survival time of 11.6 months after diagnosis. Results of immunohistochemical staining were as followed: S-100 (7/8), p53 (7/8). The Ki67/MIB-1 proliferation index was detectable in all tumour samples, it differed from 10-30%. INTERPRETATION: MPNST is a rare and fatal diagnosis in neurosurgery with high risk of local recurrence and occurence of distant metastases. Though mulitimodal therapy including surgical resection and adjuvant radiotherapy including brachytherapy is available, the prognosis remains dismal. Modern clinical studies and the development of effective chemotherapy is needed in order to gain control of the disease.

Disposal options for infectious medical waste generated during home-based dental care.

The number of dentists providing mobile care is increasing. One of the challenges the mobile dentist faces is proper handling and disposal of infectious medical waste generated during patient care. Mobile dentists must concern themselves with meeting Federal, state, and local regulations. Federal agencies that have jurisdiction over this issue are the Environmental Protection Agency (EPA) and the Occupational Safety and Health Administration (OSHA). EPA guidelines are summarized and clarified with respect to pre-transportation and transportation issues. Compliance with OSHA standards are addressed through presentation of a sample protocol for handling infectious medical waste. It is beyond the scope of this paper to discuss in detail the policies of each municipality, and practitioners are advised to consult with state and local authorities regarding proper handling and transportation of this material. Using the information presented in this paper, the mobile dentist can approach this complex issue in an organized manner.

Benign chondrolipomatous tumour of the breast.

Two patients with benign chondrolipomatous tumours of the breast were subjected to mammography. In one case this was as part of the investigation of a breast lump detected clinically, while in the other the lesion was detected during routine follow-up of a woman with long-standing cystic hyperplasia. The mammographic appearances were similar in the two cases and were unusual, each lesion showing as a circumscribed lobulate area of radiolucency containing tiny dense flecks of opacification. Mammographic and pathological findings are presented and the significance of the diagnosis discussed. Benign chondrolipomatous tumours of the breast are rare but with increase in mammography it is possible that they will present more frequently than hitherto.

The value of risk factors in screening for breast cancer.

The value of risk factors in selecting women for repeat screening for the detection of early breast cancer is considered. The screening methods used are a detailed history, clinical examination, thermography and mammography. The risk factors assessed are the effect of a personal and family history and thermography. There are 11 240 women in the series. The incidence of cancer in the no risk group is 24/5825 (0.4%), the group with one risk factor 127/3881 (3.3%) and in those with more than one factor 263/1534 (17.1%). It is suggested that the use of risk factors is sufficiently discriminating to select women for further screening over the next 10 years after an initial negative test.

Resident and parental perceptions of adolescent problems and family communications in a low socioeconomic population.

This cross-sectional survey of a low socioeconomic patient group was designed to determine the prevalence and severity of parentally perceived behavioral problems in adolescents as well as to investigate the correlation between such problems and single parenting, family communications, and medical care delivered. The sample population consisted of 79 parents and 121 teenagers selected from a family practice center. The medical record and telephone interview were the sources of information. Results include a parental perception of a high prevalence of problems with school grades (48 percent), school attendance (38 percent), and household problems (chores and sibling rivalry). Of low prevalence but high severity were perceived problems related to suicidal ideation, running away, sexual activity, and gang membership. Single-parent homes had a threefold higher incidence of behavioral problems, a greater degree of communication, and a lower use of community resources than two-parent families. None of the approximately 400 perceived behavioral problems listed by parents was found in the family physicians' master problem list. The results indicate the need for physician education of low socioeconomic and single-parent patients with regard to communication and coping style. In addition, it appears that training programs should provide more education in the care of adolescents.