A rare case of malignant glioma suspected to have arisen from a cavernous sinus

A 55-year-old woman presented with a right trigeminal dysfunction (dysesthesia) initially, followed by right oculomotor and abducens paresis lasting 1 month. Neuroimaging studies showed an enhanced mass in the right cavernous sinus extending to the trigeminal ganglion. The extraparenchymal tumor located around the right trigeminal ganglion was totally removed, except for an intracavernous lesion, by the orbitozygomatic approach. The solid tumor was completely separated from the brainstem and seemed to be a trigeminal schwannoma arising from the trigeminal ganglion or cavernous sinus at surgery. A histological examination, however, found a typical malignant glioma that consisted primarily of astrocytic tumor cells. Immunohistochemical staining showed the tumor cells stained intensely for GFAP, S-100 protein, and vimentin, but not for NFP, Schwann/2E, CD34, and CD68. The mean MIB-1 index was 12.4%. The tumor recurred after a short time, and then it rapidly disseminated into the subarachnoid space and left the cerebral hemisphere. The patient died 1 year after the initial symptoms in spite of aggressive surgery, radiation, and chemotherapy with temozolomide. There are no previous reports of a malignant glioma arising from either the cavernous sinus or the trigeminal ganglion. From the pathogenetic point of view, this malignant glioma is an extremely rare case that developed clinically and neuroradiologically from the cavernous sinus and was suspected be being derived from ectopic glial tissue.     

A case of advanced gastric cancer with obstructive jaundice due to multiple liver metastasis successfully treated with the following combination therapy of CPT-11 and cisplatin after combination therapy of paclitaxel and TS-1

A 60-year-old man, who had been admitted to another hospital with complaints of constipation, abdominal fullness and appetite loss, was referred to our hospital for further examination and therapy. The patient was diagnosed as advanced gastric cancer (type-3) with multiple liver metastasis and obstructive jaundice. He was treated with combination therapy of paclitaxel and TS-1 (60 mg/m(2)/day of paclitaxel was iv administered on day 1 and 8, and TS-1 of 80 mg/m(2)/day was orally administered for 2 weeks followed by one drug-free week), and showed a remarkable response. However, because of ascites, elevated serum CEA level and resistance in the liver metastasis and gastric region, we attempted two courses of combination therapy with high-dose CPT-11 and cisplatin (70 mg/m(2)/day of CPT-11 was administered iv on day 1 and 15, and 80 mg/m(2)/day of cisplatin on day 1 followed by two drug-free weeks) which showed a remarkable response. Two courses of combination therapy with low-dose CPT-11 and cisplatin (60 mg/m(2)/day of CPT-11 and 30 mg/m(2)/day of cisplatin were administered iv on day 1 and 15 followed by two drug-free weeks) on an outpatient basis. However, the patient showed resistance to the latter combination therapy, increased ascites due to suspicious peritonitis carcinomatosa and obvious re-growth of the metastatic tumors in the liver. He died on May 23, 2006, about ten months after initial diagnosis. We reported a case of successful treatment of combination chemotherapy for advanced gastric cancer with obstructive jaundice due to progressive multiple metastatic tumors in the liver and obtained comparative long-term survival maintaining high quality of life.     

Meta-analysis of the effects of prokinetic agents in patients with functional dyspepsia

BACKGROUND: Functional dyspepsia (FD) is often treated with prokinetic agents; however, the efficacy of prokinetic agents in patients with FD has been questioned recently. The aim of this study was to perform a meta-analysis of the effects of prokinetic agents in patients with FD. METHODS: Prokinetic agents, including metoclopramide, domperidone, trimebutine, cisapride, itopride and mosapride, used for treatment of FD between 1951 and 2005 were identified. Twenty-seven studies were selected. Difference in the probability of response between the interventional drug and placebo was used as a summary statistic for the treatment effect. Meta-regression analysis was used to detect sources of heterogeneity. RESULTS: In total, 1844 subjects were assigned to an experimental arm, and 1591 subjects were assigned to a placebo arm. Publication bias was ruled out by funnel plot and statistical testing (P = 0.975). In the overall analysis, the summary statistic was 0.295 (95% confidence interval: 0.208-0.382, P < 0.001), indicating that the interventional drug has 30% excess probability of producing a response compared with placebo. The most significant source of heterogeneity was the year of publication (P < 0.001). CONCLUSION: The data clearly indicate that prokinetic agents are significantly more effective than placebo in the treatment of FD. Although FD is a chronic condition, efficacy was assessed over short periods. Long-term randomized controlled trials are needed to confirm the effect.     

A p.D116G mutation in CREB1 leads to novel multiple malformation syndrome resembling CrebA knockout mouse

We evaluated an autopsy case with severe neonatal respiratory distress, hypoplasia of thymus, thyroid gland and cerebellum, and agenesis of the corpus callosum displaying striking phenotypic similarity to the CrebA knockout mouse. On the assumption that comparable genetic alterations must be present, we checked the whole genomic DNA sequence of cyclic adenosine monophosphate (cAMP) response element binding protein 1 (CREB1), the human counterpart of mouse CrebA, and found a missense c.347A>G mutation corresponding to p.D116G within the kinase-inducible domain (KID) of CREB1. When transcribed in vitro, while Ser-133 phosphorylation of KID was maintained upon forskolin treatment, mutated CREB1 protein failed to associate with the KIX domain of co-activator CREBBP/EP300, and thereby, interrupted cAMP-dependent protein kinase A signal transduction as the dominant-negative form. This is the first report of a sporadic CREB1-related multiple malformation syndrome that, in light of accumulated knowledge of phenotypic features in gene-targeted animals, clearly emphasizes the importance of cross-species translational research.     

NLRC4-driven production of IL-1β discriminates between pathogenic and commensal bacteria and promotes host intestinal defense

Intestinal phagocytes transport oral antigens and promote immune tolerance, but their role in innate immune responses remains unclear. Here we found that intestinal phagocytes were anergic to ligands for Toll-like receptors (TLRs) or commensals but constitutively expressed the precursor to interleukin 1β (pro-IL-1β). After infection with pathogenic Salmonella or Pseudomonas, intestinal phagocytes produced mature IL-1β through the NLRC4 inflammasome but did not produce tumor necrosis factor (TNF) or IL-6. BALB/c mice deficient in NLRC4 or the IL-1 receptor were highly susceptible to orogastric but not intraperitoneal infection with Salmonella. That enhanced lethality was preceded by impaired expression of endothelial adhesion molecules, lower neutrophil recruitment and poor intestinal pathogen clearance. Thus, NLRC4-dependent production of IL-1β by intestinal phagocytes represents a specific response that discriminates pathogenic bacteria from commensal bacteria and contributes to host defense in the intestine.     

Dynamics of the language/memory functional regions determing using ECoG and fMRI

We compared electrocorticography (ECoG) with invasive intracranial noninvasive functional MRI using language-related tasks. Twenty patients underwent bilateral implantation of subdural electrodes (more than 80 channels) for diagnosing intractable epilepsy. Before implantation of the electrodes, language-related fMRI was performed, and the fMR images were superimposed on individual brain images. Brain mapping with electrocortical stimulation was performed on the basis of the fused fMR and brain MR images, and the specificity and sensitivity of language-related fMRI was calculated. For careful interpretation of spatial and temporal ECoG changes with semantic tasks, we developed a software to visualize semantic-ECoG dynamics in the brain. Semantic-ECoG was recorded during word, figure, and face recognition as well as memory tasks. The raw ECoG data were processed by averaging and time-frequency analysis, and the functional profiles were projected onto the individual brain surface. Acquired ECoG was classified using Support Vector Machine and Sparse Logistic Regression to decode brain signals. Because of variations in electrode locations, we normalized the ECoG electrodes by using SPM8. Although fMRI has 90% sensitivity, its specificity is only up to 50%. The basal temporal-occipital cortex was activated within 250 ms after visual object presentation. Compared to other stimuli, face stimulation evoked significantly higher ECoG amplitudes. Among different brain regions, the hippocampus was predominantly activated during the memory task. The prediction rate of ECoG classification was 90%, which was sufficient for clinical use. Semantic-ECoG is a powerful technique to detect and decode human brain functions.     

Expression and functional analysis of menin in a multiple endocrine neoplasia type 1 (MEN1) patient with somatic loss of heterozygosity in chromosome 11q13 and unidentified germline mutation of the MEN1 gene

In some patients with multiple endocrine neoplasia type 1 (MEN1) it is not possible to identify a germline mutation in the MEN1 gene. We sought to document the loss of expression and function of the MEN1 gene product, menin, in the tumors of such a patient. The proband is an elderly female patient with primary hyperparathyroidism, pancreatic islet tumor, and breast cancer. Her son has primary hyperparathyroidism. No germline MEN1 mutation was identified in the proband or her son. However, loss of heterozygosity at the MEN1 locus and complete lack of menin expression were demonstrated in the proband's tumor tissue. The proband's cultured parathyroid cells lacked the normal reduction in proliferation and parathyroid hormone secretion in response to transforming growth factor- beta. This assessment provided insight into the molecular pathogenesis of the patient and provides evidence for a critical requirement for menin in the antiproliferative action of transforming growth factor-beta.     

Causal role of Helicobacter pylori infection and eradication therapy in gastric carcinogenesis

Many epidemiological reports indicate that Helicobacterpylori(H pylori)infection plays an important role ingastric carcinogenesis.Several genetic and epigeneticalterations contribute to the initiation,promotion,andprogression of the cancer cells in a multi-step manner.H pylori is known to induce chronic inflammation in thegastric mucosa.Its products,including superoxides,participate in the DNA damage followed by initiation,andthe inflammation-derived cytokines and growth factorscontribute to the promotion of gastric carcinogenesis.By eradicating H pylori,gastric inflammation can becured; the therapy diminishes the levels not onlyof inflammatory cell infiltration,but also atrophy/intestinal metaplasia in part.A randomized controlledtrial revealed that the eradication therapy diminishedthe gastric cancer prevalence in cases without pre-cancerous conditions.In addition,recent epidemiologicalstudies from Japanese groups demonstrated thatthe development of gastric cancer,especially of theintestinal type,was decreased by successful eradicationtherapy,although these were designed in a non-randomized manner.However,it should be mentionedthat endoscopic detection is the only way to evaluate thedegree of gastric carcinogenesis.We have reported thatthe endoscopic and histological morphologies could bemodified by eradication therapy and it might contributeto the prevalence of gastric cancer development.Considering the biological nature of cancer cellproliferation,it is considered that a sufficiently long-termfollow-up would be essential to discuss the anticancereffect of eradication therapy.