Analysis of Ki-67, p53 and Bcl-2 expression in the dysplasia-carcinoma sequence of Barrett's esophagus.

The grading of dysplasia in Barrett's esophagus has prognostic importance, however observer variation limits the reliability of simple histological analysis alone. We investigated Ki-67, p53 and Bcl-2 expression in Barrett's esophagus, in the sequence from Barrett's low-grade dysplasia to high-grade dysplasia and infiltrating adenocarcinoma. Forty-four esophagectomy specimens were utilized: 39 specimens with esophageal dysplasia and adenocarcinoma and 5 specimens with esophageal dysplasia only. This gave 83 sections (2 sections for specimens with dyplasia and carcinoma) examined from 44 patients. The sections were examined for Ki-67, p53 and Bcl-2 reactivity by immunohistochemistry. Low-grade dysplasia was present in 14 sections, high-grade dysplasia in 30 sections and carcinoma in 39 sections. Ki-67 expression occurred in 2 out of 14 (14%) sections with low-grade dysplasia, in 22 out of 30 (73%) sections with high-grade dysplasia and in 34 out of 39 (87%) sections with carcinoma (p<0.001). p53 protein expression was found in 1 of 14 (7%) sections with low-grade dysplasia, in 18 of 30 (60%) sections with high-grade dysplasia and in 33 of 39 (85%) sections with carcinoma (p<0.001). Expression of Bcl-2 was found in 11 of 14 (84%) sections with low-grade dysplasia but immunoreactivity was not seen in any section with high-grade dysplasia or Barrett's carcinoma. Our results indicate that overexpression of Ki-67, Bcl-2 protein and p53 mutations can be identified as early events during neoplastic progression in Barrett's esophagus. These data support the hypothesis that, in the progression of Barrett's metaplasia to adenocarcinoma, the balance of proliferation/apoptosis plays an important role.

A new mutation of E-cadherin gene in familial gastric linitis plastica cancer with extra-digestive dissemination.

Over a 12-month period, we diagnosed poorly differentiated infiltrative independent-cell gastric adenocarcinoma in two brothers and one sister aged 41 to 47 years. Their father had died from antral cancer at the age of 34 years. These cancers had two characteristic clinical features: rapid course and distant malignant dissemination. In all three patients, polymerase chain reaction-sequencing of the E-cadherin (CDH1) gene of white blood cells identified a heterozygous nonsense mutation of exon 3, producing a stop codon at position 95 (Q95X), resulting in a truncated protein. The alteration of this protein, which plays a crucial role in epithelial cell adhesion, probably explains the clinical expression in this type of familial diffuse gastric cancer.

Is chlormethiazole neuroprotective in experimental global cerebral ischemia? A microdialysis and behavioral study.

Chlormethiazole, an anticonvulsive agent, has been shown to have a possible neuroprotective effect against cerebral ischemia. In addition, chlormethiazole inhibits methamphetamine-induced release of dopamine, protecting against this neurotransmitter's neurotoxicity. The aim of this work was to ascertain whether, in experimental cerebral ischemia, chlormethiazole administration attenuated the ischemia-induced rise of the extracellular concentration of aminergic neurotransmitters and whether it reduces ischemia-induced deficits in memory and learning. Histology for assessment of ischemic damage was a so included. The four-vessel occlusion rat model was used to induce global cerebral ischemia. Aminergic neurotransmitters and their metabolites in the striatal extracellular fluid obtained by microdialysis were assayed by high-performance liquid chromatography-electrochemical detection. The drug was administered either IP (50 mg/kg-1) or directly through the dialysis probe (30 microM) 80 min before ischemia. For the behavioral test and histology, the drug was given IP (100 mg/kg-1) 1 h postischemia. The results obtained did not demonstrate any statistically significant evidence that chlormethiazole has an effect on the ischemia-induced rise in extracellular dopamine and serotonin levels. There was also no variation in metabolite levels. Behavioral measures (learning, recall) were not changed appreciably by the treatment. We observed no significant cell protection in the hippocampus (CA1, CA1), striatum, and entorhinal cortex in animals treated with chlormethiazole. We conclude that, under our experimental conditions, chlormethiazole has little or no effect on the neurochemical, neurobehavioral, and histological consequences of global cerebral ischemia.

[Crohn's disease complicated by multiple and recurrent aseptic splenic abscesses]. / Maladie de Crohn compliquée d'abcès aseptiques multiples et récidivants de la rate.

We report a case of multiple aseptic splenic abscesses occurring in a woman with Crohn's disease for three years. All microbiological samples were negative. The diagnosis was suspected on abdominal echography and CT scan and confirmed on histologic examination of the splenectomy specimen. The evolution was marked by recurrence of fever and inflammatory syndrome, associated to transitory morphological abnormalities of the accessory spleen. Aseptic splenic abscesses recurrence was suspected. This case allows us to consider aseptic splenic abscesses as an extra-intestinal manifestation and not as a splenic localisation of Crohn's disease.

Rathke's cleft cysts: surgical-MRI correlation in 16 symptomatic cases.

Rathke's cleft cysts (RCCs) are non neoplastic epithelial lesions of the sellar region that have been rarely reported as a clinical entity. We retrospectively reviewed the magnetic resonance imaging (MRI), intraoperative, and pathological findings of a series of 16 cases of RCCs operated at our institution since 1992. Concurrently, we discussed the different hypotheses about their embryological origin. The patients included 12 females and 4 males, 11 to 73 years of age. Endocrine disturbance was the most common presentation, followed by headaches and visual impairment. The location of the cyst was intrasellar in 7 cases, intrasellar and suprasellar in 6 cases, and suprasellar in 3 cases. The size of the cyst ranged from 8 to 26 mm (mean 12 mm). MRI signal intensity was quite variable on T1-weighted images. The cyst appeared hyperintense in 6 cases, hypointense in 6 cases, isointence in 3 cases, and heterogeneous in one case. On T2-weighted images (available in 13 cases), the signal intensity was more constant and appeared hyperintense in 11 cases and hypointense in 2 cases. After Gd-DTPA, we did not observe enhancement either of the cyst contents or of the cyst wall, but only of the pituitary gland in all patient. Most often, the pituitary gland was displaced inferiorly by the cyst located above showing a typical image of "an egg in a cup". Fifteen patients were operated upon via the transsphenoidal approach and one upon a frontal craniotomy. Intraoperatively, the cyst contents were gelatinous or thick, and dark colored. In 2 cases, it was cerebrospinal fluid-like corresponding to the signal observed on MRI. The position of the pituitary gland confirmed by surgery in 15 cases coincided with enhancement seen and MR imaging. In 13 cases where biopsy of the cyst wall was performed, it confirmed focally ciliated columnar or cuboid epithelium. A coexistent adenoma was found in one case. In conclusion, we consider that RCCs have varied MRI characteristics so that no pathognomonic sign may be observed. Except in few cases, there were no correlation between MRI and intraoperative findings. Therefore, even with MRI studies, differential diagnoses with others cystic lesions of the sellar region remains extremely difficult. The most interesting findings on MRI studies of RCCs were to locate the pituitary gland to help the surgeon to preserve pituitary tissue during surgery.

[Expanding mature pineal teratoma syndrome. Case report]. / Tératome mature évolutif pinéal. A propos d'un cas.

We present a case of growing teratoma syndrome of the pineal region. To our knowledge, this is the fourth case reported in the literature. A 13-year-old boy was referred for intracranial hypertension and bilateral papillary edema. CT scan showed a pineal region tumor with obstructive hydrocephalus. After CSF (cerebrospinal fluid) shunting, MRI showed that the tumor had a heterogenous signal enhancement. The tumor marker HCG (human chorionic gonadotrophin) was elevated in CSF and serum. After three cycles of chemotherapy, MRI showed an important increase in tumor size with morphologic modifications. However, HCG in CSF and serum returned to normal. Surgical resection was performed and histological examination of the whole specimen showed mature teratoma. On postoperative MRI, there was a small area of signal enhancement of the left thalamus. Radiotherapy was given. The child was in complete remission 15 months after the diagnosis. Growing teratoma syndrome is a mixed germ cell tumor with a secreting portion that responds to chemotherapy and a non secreting portion of mature teratoma that continues to grow under chemotherapy. The treatment should include chemotherapy for the malignant secreting portion and surgery for the mature teratoma.

MRI of intramedullary spinal schwannomas: case report and review of the literature.

Intramedullary spinal schwannomas are uncommon. We report a solitary cervical intramedullary schwannoma shown by MRI and treated surgically, and review 12 previous cases with MRI. MRI findings and pathogenesis are discussed.

[Gene therapy of cerebral glioblastoma by adenovirus vector. Experimental model in the rat]. / Thérapie génique du glioblastome cérébral par vecteur adénoviral. Modèle expérimental chez le rat.

Our aim was to test the therapeutic effects of adenovirus-mediated gene therapy in an animal brain tumor model which was obtained by stereotactic injection of 9L gliosarcoma cells into the caudate nucleus of rat brains. Seven days after the implantation of tumor cells, adenovirus vectors bearing the Escherichia coli beta-galactosidase gene (ADVbgal) or the herpes simplex virus thymidine kinase gene (ADVtk) were stereotactically injected into the tumor. Injection of the ADVbgal resulted in the expression of the marker gene in 11 animals. Transfer of the ADVtk was followed, 3 days later, by intraperitoneal injection of ganciclovir (GCV) for 10 days. A control group was treated with saline instead of GCV. We observed a significant regression of the tumors in the rats treated with ADVtk and GCV as compared with control animals. In four cases the tumor completely disappeared after treatment. These results demonstrate the potential efficacy of adenovirus-mediated transfer of the HSVtk gene following by GCV administration for the treatment of glioblastomas.