Incidence and clinical significance of postoperative delirium after brain tumor surgery.

BACKGROUND: Delirium is an acute and reversible deterioration of mental state. Postoperative delirium (POD) can develop after surgical procedures and is associated with impaired health status and worse recovery. So far, there is little data about postoperative delirium after brain surgery. The aim of this study was to evaluate frequency, risk factors, and prognostic value of POD in predicting short-term postoperative outcomes after brain tumor surgery. METHODS: Five-hundred and twenty-two patients who underwent elective brain tumor surgery in 2010-2017 were included in this prospective study. Patients were monitored for POD using the Confusion Assessment Method for the ICU (CAM-ICU) for 2 to 7 days after the surgery. At hospital discharge, outcomes were evaluated using the Glasgow Outcome Scale (GOS). RESULTS: POD was diagnosed in 22 (4.2%) patients. Risk factors of POD were low level of hemoglobin, poor functional status at time of admission, low education level and older age (65 years and older). POD incidence was not associated with brain tumor laterality, location, extent of resection, histological diagnosis, or affected brain lobe. POD was associated with greater risk for unfavorable outcomes at hospital discharge (OR = 5.3; 95% CI [2.1-13.4], p = 0.001). CONCLUSIONS: POD is not a common complication after elective brain tumor surgery. Older age, poor functional status, low education level and anemia are associated with greater POD risk. Extent of surgical intervention and brain tumor location are not associated with POD risk. POD is associated with worse outcome at hospital discharge.

Prognostic role of high sensitivity C-reactive protein and interleukin-6 in glioma and meningioma patients.

High sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6) can be important prognostic indicators of brain tumor patients. We investigated the association of circulating IL-6 and hsCRP concentrations with discharge outcomes and survival of glioma and meningioma patients. One-hundred and sixty-three (115 women; median age 57 years) patients admitted for meningioma (n = 94), high-grade glioma (n = 48) and low-grade glioma (n = 21) surgery were enrolled in this prospective cohort study. Serum samples were collected within 24 h of admission. Discharge outcome was evaluated using the Glasgow Outcome Scale (unfavorable outcome = score from 1 to 3). Follow-up continued until November, 2016. Elevated IL-6 (≥ 2 pg/ml) and hsCRP (≥ 1 mg/l) concentrations were present in 25 and 35% of brain tumor patients, respectively. Elevated IL-6 concentrations were associated with unfavorable outcome at hospital discharge, adjusting for brain tumor histological diagnosis, patient age and gender (OR 2.39, 95% CI 0.97-5.91, p = 0.05). Elevated hsCRP concentrations were not associated with discharge outcome (p = 0.13). In multivariate Cox regression analyses adjusted for patient age, gender, extent of tumor resection and adjuvant treatment, elevated IL-6 concentration was associated with greater mortality risk in high-grade glioma patients (OR 2.623; 95% CI 1.129-5.597; p = 0.01), while elevated hsCRP concentration was associated with greater mortality risk in meningioma patients (OR 3.650; 95% CI 1.038-12.831; p = 0.04). Elevated IL-6 concentration is associated with greater unfavorable outcome risk in brain tumor patients and with greater mortality in high-grade glioma patients, while elevated hsCRP concentration is associated with greater mortality in meningioma patients.

Preoperative low tri-iodothyronine concentration is associated with worse health status and shorter five year survival of primary brain tumor patients.

BACKGROUND: Low tri-iodothyronine syndrome is associated with worse prognosis of severely ill patients. We investigated the association of thyroid hormone levels with discharge outcomes and 5-year mortality in primary brain tumor patients. METHODS: From January, 2010 until September, 2011, 230 patients (70% women) before brain tumor surgery were evaluated for cognitive (Mini mental State Examination; MMSE) and functional (Barthel index; BI) status, and thyroid function profile. The Low triiodothyronine syndrome was defined as triiodothyronine concentration below the reference range. Unfavorable discharge outcomes were Glasgow outcome scale score of ≤3. Follow-up continued until November, 2015. RESULTS: Seventy-four percent of patients had Low triiodothyronine syndrome. Lower total tri-iodothyronine concentrations were associated with lower MMSE (p=.013) and BI (p=.023) scores independent of age, gender and histological diagnosis. Preoperative Low tri-iodothyronine syndrome increased risk for unfavorable discharge outcomes adjusting for age, gender and histological diagnosis (OR=2.944, 95%CI [1.314-6.597], p=.009). In all patients, lower tri-iodothyronine concentrations were associated with greater mortality risk (p≤.038) adjusting for age, gender, extent of resection, adjuvant treatment and histological diagnosis. The Low tri-iodothyronine syndrome was associated with greater 5-year mortality for glioma patients (HR=2.197; 95%CI [1.160-4.163], p=.016) and with shorter survival (249 [260] vs. 352 [399] days; p=.029) of high grade glioma patients independent of age, gender, extent of resection and adjuvant treatment. CONCLUSIONS: The Low tri-iodothyronine syndrome is common in brain tumor patients and is associated with poor functional and cognitive status, and with worse discharge outcomes. The Low tri-iodothyronine syndrome is associated with shorter survival of glioma patients.

Digit ratio (2D:4D) in primary brain tumor patients: A case-control study.

BACKGROUND: The second-to-fourth digit ratio (2D:4D) reflects prenatal estrogen and testosterone exposure, and is established in utero. Sex steroids are implicated in development and progression of primary brain tumors. AIMS: To investigate whether there is a link between 2D:4D ratio and primary brain tumors, and age at presentation. METHODS: Digital images of the right and left palms of 85 primary brain tumor patients (age 56.96±13.68years; 71% women) and 106 (age 54.31±13.68years; 68% women) gender and age matched controls were obtained. The most common brain tumor diagnoses were meningioma (41%), glioblastoma (20%) and pituitary adenoma (16%). Right and left 2D:4D ratios, and right minus left 2D:4D (Dr-l) were compared between patients and controls, and were correlated with age. RESULTS: Right and left 2D:4D ratios were significantly lower in primary brain tumor patients relative to controls (t=-4.28, p<0.001 and t=-3.69, p<0.001, respectively). The Dr-l was not different between brain tumor patients and controls (p=0.27). In meningioma and glioma patients, age at presentation correlated negatively with left 2D:4D ratio (rho=-0.42, p=0.01 and rho=-0.36, p=0.02, respectively) and positively with Dr-l (rho=0.45, p=0.009 and rho=0.65, p=0.04, respectively). CONCLUSIONS: Right and left hand 2D:4D ratios are lower in primary brain tumor patients relative to healthy individuals suggesting greater prenatal testosterone and lower prenatal estrogen exposure in brain tumor patients. Greater age at presentation is associated with greater Dr-l and with lower left 2D:4D ratio of meningioma and glioma patients. Due to small sample size our results should be considered preliminary and interpreted with caution.

Suicidal ideation in patients undergoing brain tumor surgery: prevalence and risk factors.

PURPOSE: Suicidal ideation (SI) is an important complication in cancer patients that should be promptly recognized and adequately managed. We investigated the prevalence rate and correlates of pre-operative SI in brain tumor (BT) patients admitted for elective BT surgery. METHODS: Two hundred and eleven consecutive patients (70 % women; mean age 55.9 ± 15.4 years) scheduled for BT surgery were evaluated for SI ("suicidal thought" item from the Beck Depression Inventory-II), depressive/anxiety symptom severity (Hospital Anxiety and Depression scale (HADS)), health-related quality of life (SF-36 scale), functional status (Barthel Index), and psychiatric histories and treatments. The majority of patients were diagnosed with meningioma (39 %) and high-grade glioma (17 %). RESULTS: SI was self-reported by 12 (6 %) patients. Patients expressing SI were most commonly diagnosed with meningioma (50 %). Patients with SI were more likely to have a past history of psychiatric disorders, scored higher on the HADS anxiety subscale, and reported worse health-related quality of life across physical and mental health domains. In multivariate regression analyses, worse perceived mental health was associated with increased risk for SI independently from clinical, sociodemographic, and other patient-oriented variables considered in the study. CONCLUSIONS: SI was self-reported by 6 % of BT patients before surgical intervention and was associated with a past history of psychiatric disorders and worse perceived health status. Poor mental health was an independent correlate of SI. The perception of health status by a patient should be considered as an important determinant of poor mental health in BT patients.

Predictors of health-related quality of life in neurosurgical brain tumor patients: focus on patient-centered perspective.

BACKGROUND: In brain tumor (BT) patients, the association between health-related quality of life (HRQoL) and psychological characteristics remains largely unknown. We evaluated the association of personality traits, clinical factors, psychological distress symptoms, and cognitive state with HRQoL in BT patients. METHODS: On admission for BT surgery, 200 patients (69 % women; age 55.8 ± 14.5 years) were evaluated for HRQoL (SF-36 scale), Big-Five personality traits (Ten-Item Personality Inventory), psychological distress symptoms (Hospital Anxiety and Depression Scale or HADS), cognitive function (Mini-Mental State Examination or MMSE) and clinical characteristics, including functional status (Barthel index or BI). The most common BT diagnoses were meningioma (39 %) and high-grade glioma (18 %). RESULTS: Only factors significantly associated with SF-36 domains in univariable regression analyses were included in their respective multivariable models and predicted from 6 %-49 % of the total variance of SF-36 scores. Greater TIPI emotional stability score was independently associated with greater SF-36 emotional well-being (ß = 0.23, p < 0.001) and general health (ß = 0.18, p = 0.01) scores, and greater TIPI consciousness score, with greater SF-36 emotional well-being score (ß = 0.13, p = 0.02). HADS-anxiety and HADS-depression scores were the strongest independent determinants of all, except physical functioning, SF-36 scores (ß-values range from 0.14 to 0.56; p values ≤ 0.03). BI score was the strongest independent determinant of SF-36 physical functioning score (ß = 0.36, p < 0.001). MMSE score was associated with all but emotional well-being and social functioning SF-36 scores. CONCLUSIONS: Consciousness and emotional stability should be considered important personality-related determinants of HRQoL in BT patients. Psychological distress, functional disability, and cognitive impairment are also important predictors of HRQoL.

Low triiodothyronine syndrome as a predictor of poor outcomes in patients undergoing brain tumor surgery: a pilot study: clinical article.

OBJECT: A low triiodothyronine (T3) state is highly prevalent and is associated with a poor prognosis in critically ill patients. The authors investigated, in patients undergoing brain tumor surgery, the direct association of a perioperative low T3 syndrome with clinical outcomes and also with symptoms of depression and anxiety. METHODS: Ninety consecutive patients (71% women, median age 55 years), on admission for brain tumor surgery, were evaluated for sociodemographic and clinical characteristics. Their thyroid function profile was assessed on the morning of brain tumor surgery and on the morning after brain tumor surgery. Patients with free T3 concentrations of 3.1 pmol/L or less were considered to have low T3 syndrome. The patients were evaluated for symptoms of depression and anxiety using the Hospital Anxiety and Depression Scale (HADS) before and after surgery and for clinical outcomes using the Glasgow Outcome Scale (GOS) at discharge. RESULTS: After brain tumor surgery, free T3 concentrations decreased (p < 0.001) and the proportion of patients with low T3 levels increased from 38% to 54% (p = 0.02). Lower preoperative (rho = 0.30, p = 0.004) and postoperative (rho = 0.33, p = 0.002) free T3 concentrations correlated with low GOS scores at discharge. Preoperative low T3 syndrome (OR 5.49, 95% CI 1.27-23.69, p = 0.02) and postoperative low T3 syndrome (OR 8.73, 95% CI 1.49-51.21, p = 0.02) both increased risk for unfavorable clinical outcomes (GOS scores < 5) at discharge, after adjusting for age, sex, histological diagnosis of brain tumor, preoperative functional impairment, previous treatment for brain tumor, and depressive symptoms. Preoperative low T3 syndrome increased the risk for preoperative (HADS-depression subscale score ≥ 11; OR 4.12, 95% CI 1.16-14.58, p = 0.03) but not postoperative depressive symptoms independently from sociodemographic and clinical factors. CONCLUSIONS: Low T3 syndrome is a strong independent predictor of unfavorable clinical outcomes and depressive symptoms, and its diagnosis and preoperative management should be considered in patients undergoing neurosurgery for the treatment of brain tumors.

Screening for psychological distress in neurosurgical brain tumor patients using the Patient Health Questionnaire-2.

OBJECTIVE: Psychological distress is highly prevalent but often undiagnosed in brain tumor patients. We evaluated the psychometric properties of the Patient Health Questionnaire-2 (PHQ-2) for screening of distressed neurosurgical brain tumor patients. METHODS: A total of 226 (69% women; mean age 55.6 ± 14.7 years) consecutive patients on admission for elective brain tumor surgery were evaluated for psychological distress using the PHQ-2, the Hospital Anxiety and Depression Scale (HADS; n = 206), and the Beck Depression Inventory-II (BDI-II; n = 196). At discharge, the patients were reevaluated using the PHQ-2 and HADS. RESULTS: On admission, 43% and 18% of patients had moderate-severe psychological distress according to the HADS (HADS depression or anxiety score ≥ 11) and BDI-II (score ≥ 20), respectively. At discharge, there was a significant decrease in psychological distress among patients according to the PHQ-2 (p = 0.04) and HADS (p < 0.001) screening results. The PHQ-2 had marginal internal consistency (Cronbach's coefficient alpha = 0.68) and suboptimal test-retest reliability (intraclass correlation coefficient = 0.51). The PHQ-2 had acceptable psychometric properties for identifying patients with moderate-severe psychological distress according to the HADS (sensitivity = 74%, specificity = 68%, and positive predictive value (PPV) = 40%) and BDI-II (sensitivity = 71%, specificity = 65%, and PPV = 30%). Psychometric properties of the PHQ-2 were inferior for mild-severe psychological distress. Greater number of PHQ-2 depressive symptoms was associated with greater scores on the HADS and BDI-II (all ps < 0.001). CONCLUSIONS: Psychological distress is prevalent in brain tumor patients and can be successfully identified using the PHQ-2. The PHQ-2 has moderate internal consistency. The PHQ-2 should be considered for routine use in brain tumor patients for psychological distress screening purposes.

Evaluation of health-related quality of life in Lithuanian brain tumor patients using the EORTC brain cancer module.

BACKGROUND AND OBJECTIVE. Health-related quality of life (HRQoL) is considered an important outcome measure in neuro-oncology. The aim of this study was to evaluate the psychometric properties of the brain cancer-specific Quality of Life Questionnaire (QLQ-BN20) of the European Organization for Research and Treatment of Cancer (EORTC) in Lithuanian brain tumor patients. MATERIAL AND METHODS. One hundred consecutive patients (71% of women; mean age, 58 ± 14 years) admitted for elective brain tumor surgery were evaluated for HRQoL using the QLQ-BN20, QLQ-C30 (a core EORTC questionnaire for cancer patients), and SF-36 scale; for motor dysfunction (clinical examination); for cognitive dysfunction (Mini-Mental State Examination); and for disability (Barthel Index). RESULTS. The QLQ-BN20 subscales had an adequate internal consistency (Cronbach α, 0.75-0.90). Motor dysfunction on neurological examination was associated with greater motor dysfunction on the QLQ-BN20; greater disability, with greater future uncertainty, motor dysfunction, communication deficits, headaches, seizures, drowsiness, itchy skin, weakness of legs, and poor bladder control on the QLQ-BN20; and cognitive dysfunction, with greater future uncertainty, visual deficits, motor dysfunction, communication deficits, headaches, drowsiness, and weakness of legs symptoms on the QLQ-BN20, suggesting an adequate clinical validity of the QLQ-BN20. A score for motor dysfunction on the QLQ-BN20 correlated with a score for motor dysfunction on the QLQ-C30 and SF-36 scales; a score for headache on the QLQ-BN20, with a score for pain on the QLQ-C30 and SF-36 scales; and a score for drowsiness symptoms on the QLQ-BN20, with a score for fatigue on the QLQ-C30. CONCLUSIONS. The Lithuanian version of the EORTC-QLQ-BN20 scale has acceptable psychometric properties and can be reliably used for the assessment of HRQoL in brain tumor patients.

A primary primitive neuroectodermal tumor of the central nervous system in a 51-year-old woman: a case report and literature review.

Primitive neuroectodermal tumors are a group of rare, aggressive, and highly malignant embryonal tumors of unknown etiology of the central and peripheral nervous systems. It is a term for a group of small round cell tumors thought to be derived from fetal neuroectodermal precursor cells. Primitive neuroectodermal tumor is usually described as a tumor of children younger than 15 years and is very rare in adults. The article presents a short literature review and a rare case of a primary primitive neuroectodermal tumor of the central nervous system diagnosed in a 51-year-old woman.

Tumor grade-related NDRG2 gene expression in primary and recurrent intracranial meningiomas.

Approximately 30% of all primary CNS tumors are meningiomas. Depending on histological type, meningiomas can recur as follows: benign--with five-year recurrence of 5%, atypical--recurrence approximately 40%, and anaplastic with recurrence of 50-80%. In an attempt to understand the molecular mechanism of meningioma recurrence we investigated the N-Myc downstream-regulated gene 2 (NDRG2), which has recently been described as important in suppressing cellular carcinogenesis in different types of cancer. The objective of the study was to investigate NDRG2 gene expression at the mRNA level in primary and recurrent meningiomas as a potential marker of tumor aggressiveness, malignancy, and recurrence. Primary and recurrent meningiomas of WHO grades I, II, and III from 35 patients operated on between 2005 and 2008 year at the Department of Neurosurgery of Kaunas Medical University Hospital (Lithuania) were studied. Using the qRT-PCR method we measured NDRG2 gene expression at the mRNA level in primary (n = 24) and recurrent (n = 11) meningiomas. Statistically significant differences in NDRG2 gene expression level were observed between primary and recurrent meningioma groups (P < 0.05) and between benign (WHO grade I) and atypical (WHO grade II) meningiomas (P < 0.05). No statistically significant differences were observed (P > 0.05) among histological subtypes of benign (WHO grade I) meningiomas: fibrous, meningothelial, and transitional. In accordance with our results, reduction of NDRG2 gene expression at the mRNA level could help to explain malignant progression and predisposition to recurrence in meningiomas.

Environmental factors and breast cancer.

This review summarizes the results of studies on the effects of environment on breast cancer risk. As known risk factors such as reproductive life, inheritance, and socioeconomic status are estimated to explain only about half of the breast cancer cases, it has been thought that environmental factors could also be related to the risk of this disease. It is known that ionizing radiation is an environmental risk factor increasing the risk of breast cancer. The data of experimental studies show that some organochlorines could be associated with breast cancer risk although the data from epidemiological studies are not consistent due to the difficulties to assess exposure and other risk factors. Recent experimental studies show that cadmium is an environmental factor that mimics the effects of estradiol in estrogen-responsive breast cancer cell lines while solar radiation possibly decreases the risk due to protective effect of vitamin D. The data on the effect of electromagnetic fields are not consistent. Although evidence about the effect of environmental factors on the risk of breast cancer is not convincing, some of these factors together with inheritance, reproductive life, and age at exposure could be associated with an increased risk of the disease.