Potential clinical role of telomere length in human glioblastoma.

Glioblastoma Multiforme (GBM) is the most common and lethal of human primary central nervous system (CNS) tumors. Due to the tumour's intrinsic clinical and molecular heterogeneity, choice of initial treatment, prediction of survival, stratification of patients, prediction and monitoring of response to therapy, represent some of the greatest challenges in the management of GBM patients. Patients, despite optimal surgery, radiation and chemotherapy, still have a median survival of 14-16 months. A reason for this dismal prognosis is because of the relative inaccuracy of current prognostic markers, so far based on clinical or pathological variables. Molecular markers that effectively predict response to therapy and survival outcomes are limited. Consequently, there is a strong need to develop novel and independent markers of prognosis. Ideal biomarkers for solid tumors would serve one or more important functions. Telomeres, guanine-rich tandem DNA repeats of the chromosomal end, provide chromosomal stability, regulates important cellular processes, and seem to be implicated in human carcinogenesis. Recently, telomeres have been shown either to be associated with clinical markers of disease progression or to be independent markers of cancer prognosis in solid tumours, including GBM. Nevertheless, a corresponding comprehensive discussion of these promising developments in brain tumours has not yet been available in the literature. Therefore, here we reviewed studies focused on the assessment of telomeric length in brain tumours with the aim to emphasized those findings indicating a potential clinical role of telomeres in GBM. With the aim to enhance the awareness of the potential clinical role of telomeres' length information in GBM, using a southern blot analysis, telomeric length in excised tumour samples was analyzed. Moreover, an attempt to correlated telomere length with patients' overall survival, was also performed. The findings here reviewed shows some contradictory results, due to different tissues used as controls, but mainly to cellular and molecular heterogeneity in GBMs that drive molecular mechanisms controlling telomere length, included telomerase and Alternative Lengthening of Telomeres (ALT), through multiple mechanisms. However, overall these studies, including our own, are consistent with the hypothesis that GBMs' telomeres were always shorter when compared with Normal Brain Tissue (NBT), and together with higher telomerase activity seem to be associated with malignancy and poor outcome; while tumours with ALT phenotype have longer telomeres, "less malignant" behaviour and better prognosis. We conclude that, although not entirely consistent in the type of telomere alteration, i.e., attrition vs. elongation, and unclear on the underlying mechanisms, multiple studies in brain tumours have shown that telomere dysfunctions are associated with parameters of clinical outcome in patients with GBMs and therefore will be part of novel risk assessment and prognostic modalities for patients with these still dismal disease.

Endometrial thickness measurement for detecting endometrial cancer in women with postmenopausal bleeding: a systematic review and meta-analysis.

OBJECTIVE: To estimate the accuracy of endometrial thickness measurement in the detection of endometrial cancer among women with postmenopausal bleeding with individual patient data using different meta-analytic strategies. DATA SOURCES: Original data sets of studies detected after reviewing the included studies of three previous reviews on this subject. An additional literature search of published articles using MEDLINE databases was preformed from January 2000 to December 2006 to identify articles reporting on endometrial carcinoma and sonographic endometrial thickness measurement in women with postmenopausal bleeding. METHODS OF STUDY SELECTION: We identified 90 studies reporting on endometrial thickness measurements and endometrial carcinoma in women with postmenopausal bleeding. TABULATION, INTEGRATION, AND RESULTS: We contacted 79 primary investigators to obtain the individual patient data of their reported studies, of which 13 could provide data. Data on 2,896 patients, of which 259 had carcinoma, were included. Several approaches were used in the analyses of the acquired data. First, we performed receiver operator characteristics (ROC) analysis per study, resulting in a summary area under the ROC curve (AUC) calculated as a weighted mean of AUCs from original studies. Second, individual patient data were pooled and analyzed with ROC analyses irrespective of study with standardization of distributional differences across studies using multiples of the median and by random effects logistic regression. Finally, we also used a two-stage procedure, calculating sensitivities and specificities for each study and using the bivariate random effects model to estimate summary estimates for diagnostic accuracy. This resulted in rather comparable ROC curves with AUCs varying between 0.82 and 0.84 and summary estimates for sensitivity and specificity located along these curves. These curves indicated a lower AUC than previously reported meta-analyses using conventional techniques. CONCLUSION: Previous meta-analyses on endometrial thickness measurement probably have overestimated its diagnostic accuracy in the detection of endometrial carcinoma. We advise the use of cutoff level of 3 mm for exclusion of endometrial carcinoma in women with postmenopausal bleeding.

Assistance of intraoperative microvascular Doppler in the surgical obliteration of spinal dural arteriovenous fistula: cases description and technical considerations.

BACKGROUND: Intraoperative microvascular Doppler may be valuable in assisting in the surgical obliteration of dural arteriovenous fistula of the spinal cord. It enables identification, through flow spectrum analysis, of the anatomic components and haemodynamic features of this type of vascular malformation. METHODS: In two cases, intraoperative microvascular Doppler was used to assist in the surgical obliteration of dural arteriovenous fistula of the spinal cord. The fistulas were identified prior to the dura opening, and for this only minimally invasive surgery was required. Direct recordings of the arterialised draining vein and the nidus of the fistula demonstrated a pathological spectrum caused by the arterial supply and the disturbed venous outflow in which a high-resistance flow pattern and low diastolic flow resembling an arterial-like flow velocity were observed. FINDINGS: The fistulas were obliterated by interruption of the draining vein, and Doppler measurements provided information on flow velocity changes in the medullary veins from an arterial to a venous pattern. The absence of any residual flow in the draining vein confirmed successful haemodynamic treatment. INTERPRETATION: Intraoperative microvascular Doppler recording is valuable assistance in surgical closure of spinal arteriovenous fistula.

Intraoperative microvascular Doppler monitoring of blood flow within a spinal dural arteriovenous fistula: a precious surgical tool. Case report.

The authors describe a case of spinal arteriovenous fistula (AVF) treated by a microvascular Doppler-assisted surgical interruption of the arterialized vein. Microvascular Doppler monitoring represents a valid, widely available, noninvasive tool that enables identification, through flow spectrum analysis, of components of this type of vascular malformation. In this case because the location of the fistula was identified prior to opening the dura only minimally invasive surgery was required. Direct recordings of the arterialized draining vein and the nidus of the fistula demonstrated a pathological spectrum caused by the arterial supply and the disturbed venous outflow in which a high-resistance flow pattern and low diastolic flow resembling an arterial-like flow velocity were observed. The fistula was obliterated by interruption of the draining vein, and Doppler measurements provided information on flow velocity changes in the medullary veins from an arterial to a venous pattern. The absence of any residual flow in the AVF confirmed successful hemodynamic treatment. Intraoperative microvascular Doppler recording during surgical closure of spinal AVF is a widely available and reliable monitoring modality that helps to produce excellent clinical results.

Microsurgical excision of a primary isolated hypothalamic eosinophilic granuloma. Case report.

Solitary focal eosinophilic granuloma (EG) is one element in the spectrum of diseases associated with Langerhans' cell histiocytosis (LCH). This report documents the occurrence of a primary isolated hypothalamic EG in a man who presented with diabetes insipidus and panhypopituitarism. His treatment consisted of complete microsurgical excision of the lesion. After a 13-month follow-up period, no residual tumor was evident on magnetic resonance imaging and no other lesions were present in peripheral tissues. This case is unique in several respects: 1) it is the third documented case of a primary isolated hypothalamic LCH granuloma diagnosed in a living patient; 2) it is the only known example of complete microsurgical excision of such a lesion in the hypothalamic region; and 3) it demonstrates the efficacy of direct surgery in this scenario, as compared with other treatment modalities such as biopsy and irradiation, suggesting that complete surgical excision may represent the treatment of choice for isolated intracerebral LCH granulomas, being curative in most instances. Also, the literature is reviewed for information about the diagnosis and treatment of this particular type of unifocal brain lesion.

Ultra-sonografia seriada do endométrio e da endocérvice durante o ciclo menstrual normal da mulher / Serial ultrasonography of the endometrium and endocervix during the normal menstrual cycle of women

Os relatos ultra-sonográficos do endométrio humano säo, em sua maior parte, obtidos de pacientes com esterilidade conjugal, nulíparas, fazendo uso de drogas indutoras da ovulaçäo. Essas pesquisas, geralmente, näo se acompanham do estudo histológico da cavidade uterina e preocupam-se, sobretudo, com o período ovulatório. Há, contudo, controvérsias na interpretaçäo das imagens. OBJETIVO. Estudas a ultra-sonografia do endométrio, no decorrer do ciclo menstrual normal. MÉTODOS. Os autores selecionaram 15 mulheres, eumenorréicas, multíparas, que näo faziam uso de drogas indutoras da ovulaçäo, DIU ou contra-conceptivos hormonais. todas foram examinadas no primeiro, no sétimo, no décimo-quarto eno vigésimo-primeiro dia do ciclo menstrual. Confrontaram-se os achados ecográficos com os resultados histológicos. RESULTADOS. Avaliaram a imagem ultra-sonográfica do endométrio em 66.66 por cento das mulheres no primeiro dia do ciclo. Em todas elas, no sétimo, décimo-quarto e vigésimo-primeiro dia essa imagem também pôde ser identificada e apreciada. Verificaram, durante o ciclo, aumento progressivo da espessura da imagem endometrial, de forma linear. O halo hipoecóico teveincidência progressiva, atingindo 93,33 por cento no vigésimo-primeiro dia do ciclo. CONCLUSÄO. As alteraçöes cíclicas do endométrio foram demonstradas pela ultra-sonografia. As modificaçöes endocervicais também foram detectadas. Todavia, säo menos exuberantes do que as observadas no endométrio

[Serial ultrasonography of the endometrium and endocervix during the normal menstrual cycle in women]. / Ultra-sonografia seriada do endométrio e da endocérvice durante o ciclo menstrual normal da mulher.

Articles on ultrasound of the human endometrium are in the majority of the cases based on studies of patients who have infertility and are taking drugs to induce ovulation. Such investigations do not include histological study of the endometrium and have focused on the ovulatory period. There is controversy in the interpretation of the images. PURPOSE--To evaluate the sonographic appearance of the endometrium during the normal menstrual cycle. METHODS--We studied 15 multiparous women with normal cycles, and who were not under drugs for ovulation induction, had neither IUD, nor were having oral hormonal contraceptives. They were seen on the first, seventh, fourteenth, and twentieth-first days of the menstrual cycle. The sonographic aspects were compared with the histological findings. RESULTS--We could see the images of the endometrium on the first day of the cycle in 66.66% of the patients. On the other visits we could study properly its features very well in all the patients. The endometrial image thickness increased in a linear pattern and the hypoechogenic halo was seen in 93.33% of the patients on the twentieth-first day of the menstrual cycle. CONCLUSION--The cyclic changes of the endometrium were shown with the sonography. The cyclic changes of the endocervix were evaluated too with the sonogram although they are not as remarkable as the endometrial ones.