Biomedical subjects

Nicolas De Tribolet

Publications and source records attributed to Nicolas De Tribolet.

5 recordsLinked to original sources

PubMed2006

Surgery for large vestibular schwannomas: how patients and surgeons perceive quality of life.

OBJECT: The aim of this study was to assess the consequences of total removal of a large vestibular schwannoma on the patient's symptoms and quality of life (QOL). METHODS: A questionnaire regarding preoperative and postoperative symptoms with measures of both daily and global QOL and a modified 36-Item Short Form Health Survey (SF-36) QOL instrument were sent to 103 patients who had undergone surgery via a retrosigmoid approach for total removal of a Grade III or IV vestibular schwannoma. In addition, 48 patients underwent follow-up clinical examinations to assess their conditions. Seventy-two of the 103 patients completed and returned the questionnaire. Forty-six (64%) of the schwannomas were Grade IV and 26 (36%) were Grade III. The patients' pre- and postoperative symptoms were similar to those reported in other studies. The patients' perceptions of facial movement were likely to be worse than the clinicians' estimation based on the House-Brackmann classification. All scores in the QOL categories were significantly reduced when compared with normative data. Patients with large vestibular schwannomas had lower scores in all SF-36 categories except pain compared with data from other studies. Psychological problems were the preponderant symptoms, and their presence was the most powerful predictive variable for global and daily QOL. CONCLUSIONS: Surgery for a large vestibular schwannoma has a significant impact on the patient's QOL. To improve QOL postoperatively, the patient should be prepared and well informed of the consequences of such a surgery on QOL. Clinicians must be aware that early involvement of a clinical psychologist may be very helpful.

Activities of Daily Living↗

PubMed2005

Apoplexy in pituitary macroadenoma: eight patients presenting in 12 months.

Pituitary apoplexy is an ill-defined clinical entity. Some authors include hypoxic pituitary infarction, even in the absence of tumor after hemorrhagic delivery, whereas others apply this term strictly to hemorrhage within a pituitary adenoma. We conducted the present study to establish the prevalence, clinical characteristics, and outcome of pituitary apoplexy, defined as an endocrine crisis characterized by acute intense headache, with or without altered consciousness, rapid development of visual or motor ocular disorders, and pituitary failure, associated with a large pituitary adenoma. We describe 8 consecutive patients (1 woman and 7 men, aged 29-66 yr) presenting over 12 months with pituitary apoplexy. We reviewed patient charts for symptoms, imaging characteristics, hormonal data, management, pathologic findings, and outcome. We examined our pituitary tumors database for cases of macroadenoma without apoplexy occurring during the same period. In 5 patients, potential precipitating factors were present. In 6 patients (3 nonsecreting tumors, 1 free-alpha-subunit-secreting tumor, 1 growth hormone and prolactin-secreting tumor with acromegaly, and 1 prolactinoma), no pituitary disease was suspected before the acute event, representing 19% of newly diagnosed pituitary macroadenomas during the same period of time, a higher proportion than expected from our previously published series. The 2 other patients had known pituitary macroadenomas, a nonsecreting tumor and a prolactinoma on dopamine agonist therapy. Pituitary insufficiency at diagnosis included adrenal failure in 4 patients. Transsphenoidal tumor removal was performed 3-9 days after the onset of symptoms (mean, 5.3 d) in 7 of the 8 patients. Pathologic analysis disclosed tumor hemorrhage in 4 cases, ischemic necrosis in 2, and ischemia after intrasellar hemorrhage in 1. Preoperative magnetic resonance imaging was more sensitive than computed tomography for identifying hemorrhage. The newly diagnosed prolactinoma was treated with dopamine agonist. Complete neuro-ophthalmic recovery was observed in all cases, but only 2 patients displayed normal pituitary function on follow-up. The other 6 patients required long-term hormone replacement therapy. These data show that early surgical decompression prevents persistent neuro-ophthalmic deficit, but does not prevent persistent pituitary insufficiency. Moreover, published data indicate that the efficacy of surgery for the relief of neuro-ophthalmic symptoms decreases with increasing syndrome duration. Our data confirm that apoplexy occurs most often as the inaugural manifestation of pituitary macroadenoma, and suggest a recent increase of cases of apoplexy in our area.

Adenoma↗

PubMed2004

INK4a/Arf is required for suppression of EGFR/DeltaEGFR(2-7)-dependent ERK activation in mouse astrocytes and glioma.

Amplification of the epidermal growth factor receptor (EGFR) or expression of its constitutively activated mutant, DeltaEGFR(2-7), in association with the inactivation of the INK4a/Arf gene locus is a frequent alteration in human glioblastoma. The notion of a cooperative effect between these two alterations has been demonstrated in respective mouse brain tumor models including our own. Here, we investigated underlying molecular mechanisms in early passage cortical astrocytes deficient for p16(INK4a)/p19(Arf) or p53, respectively, with or without ectopic expression of DeltaEGFR(2-7). Targeting these cells with the specific EGFR inhibitor tyrphostin AG1478 revealed that phosphorylation of ERK was only abrogated in the presence of an intact INK4a/Arf gene locus. The sensitivity to inhibit ERK phosphorylation was independent of ectopic expression of DeltaEGFR(2-7) and independent of the TP53 status. This resistance to downregulate the MAPK pathway in the absence of INK4a/Arf was confirmed in cell lines derived from our mouse glioma models with the respective initial genetic alterations. Thus, deletion of INK4a/Arf appears to keep ERK in its active, phosphorylated state insensitive to an upstream inhibitor specifically targeting EGFR/DeltaEGFR(2-7). This resistance may contribute to the cooperative tumorigenic effect selected for in human glioblastoma that may be of crucial clinical relevance for treatments specifically targeting EGFR/DeltaEGFR(2-7) in glioblastoma patients.

Animals↗

PubMed2004

Non-functioning pituitary carcinoma.

Null-cell carcinomas of the pituitary are extremely rare. We describe a 41-year-old woman with a large adenohypophyseal neoplasm presenting as a primary nonfunctioning tumor without pituitary insufficiency. Signs of mass effect with progressive unilateral ocular motility disorders and anterior pituitary failure developed rapidly. Histopathological examination of the trans-sphenoidally removed tumor showed a primary pituitary null cell tumor with high mitotic index. Pituitary carcinoma was suspected because of rapid relapse of ocular motility disorders and of intra-sellar tumor growth after surgery. Radiotherapy of the sellar and parasellar area with a total dose of 59.4 Gy was performed, achieving marked tumor reduction and a significant improvement of ocular motility disorders. However, 6.5 months after presentation the patient rapidly declined and died of carcinomatous meningitis. Less than 100 pituitary carcinomas have been published so far, most of them as single-case reports, and endocrine, immunohistochemical, and ultrastructural data have not been described in the majority of cases. At presentation, there are no specific symptoms that allow to distinguish benign from malignant tumor. Prognosis is poor, since no curative treatment has been established, but aggressive surgery and radiotherapy has been recommended. Our case highlights the poor prognosis of nonfunctioning pituitary carcinomas.

Adult↗

PubMed2002

Unlabelled iododeoxyuridine increases the rate of uptake of [125I]iododeoxyuridine in human xenografted glioblastomas.

5-Iodo-2'-deoxyuridine (IdUrd), a thymidine (TdR) analogue, can be radiolabelled with iodine-125, an Auger radiation emitter, to provoke double-strand breaks once incorporated into DNA of cancer cells. We have previously shown that co-incubation of [125I]IdUrd with unlabelled IdUrd provided an additive cytotoxicity in two human glioblastoma cell lines. This observation was unexpectedly correlated with an increase in the rate of DNA incorporation of [125I]IdUrd. Here, we further evaluated the effects of unlabelled IdUrd on the uptake of [125I]IdUrd in vitro and in vivo in mice xenografted with three human glioblastoma lines. The results showed that, in these three glioblastoma lines, unlabelled IdUrd increased the rate of uptake of [125I]IdUrd in vitro by 2- to 4.4-fold and in vivo by 1.5- to 2.8-fold. The rate of uptake of [125I]IdUrd in normal rapidly dividing tissues was also increased by 1.3- to 2.8-fold. TdR completely blocked [125I]IdUrd uptake in tumours and tissues. Analogues of IdUrd, such as deoxyuridine and 5-iodo-1,3-dimethyuracil, did not reproduce the effect of IdUrd on the uptake of [125I]IdUrd, suggesting that it is not related to protection against [125I]IdUrd degradation. It is concluded that combined administration of unlabelled IdUrd may improve the use of radiolabelled IdUrd for cancer diagnosis or therapy.

Animals↗