[The Efficacy of the Emergent Shunt-Clamp System for Secondary Hydrocephalus Associated with Fourth Ventricle Outlet Obstruction Syndrome:A Report of Two Cases].

Endoscopic third ventriculostomy(ETV)is the first-line treatment for fourth ventricle outlet obstruction(FVOO)-associated hydrocephalus. However, because FVOO is difficult to diagnose in the acute stage, ventriculoperitoneal shunt(VPS)is also used. Herein, we report two cases of shunted FVOO resulting in overdrainage or slit ventricle syndrome(SVS)that were treated successfully with the shunt-clamp system. In addition, we discuss the efficacy of the shunt-clamp system for FVOO-associated hydrocephalus. CASE 1:A 79-year-old man complained of severe postural headaches. One year earlier, he underwent VPS for secondary hydrocephalus associated with hemorrhagic cerebellar infarction. CT revealed that the ventricle had become slit-like. Although the shunt valve adjusted the maximum pressure, his complaint and the ventricle shape did not improve. After the on-off valve was inserted in the shunt system and clamped, his symptoms were resolved and the ventricle size was normalized. CASE 2:A 21-year-old man who complained of drowsiness, diplopia, and severe intermittent retroocular pain was admitted to our hospital. One year earlier, he underwent VPS with the shunt-clamp system for a secondary hydrocephalus after surgery for medulloblastoma. CT on admission revealed ventricle dilatation;however, the shape of the ventricle became slit-like 3 days after admission. We made a diagnosis of SVS and planned ETV. Owing to the difficulty in approaching the lateral ventricle, the shunt system was clamped 8 hours before the operation. After confirming ventricle dilatation, ETV was successfully performed. After the operation, the symptoms were resolved, and magnetic resonance imaging confirmed that the ventricle size was normalized.

5-Aminolevulinic acid-mediated photodynamic therapy can target human glioma stem-like cells refractory to antineoplastic agents.

BACKGROUND: Glioblastoma (GBM) is a highly malignant lethal brain cancer. Accumulated evidence suggests that elevated resistance of GBM to both chemo- and radio-therapy is, at least in part, due to the presence of a small population of glioma stem cells (GSC). In the present study, we aimed to determine the sensitivity of GSCs to 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT). METHODS: For this purpose, we established GSC-enriched cell cultures (termed glioma stem-like cells or GSLCs) from A172 human GBM cell line. Under our cultivation conditions, GSLCs formed floating spheroid clusters that contained increased population of CD133/Sox2 expressing cells. Firstly, to compare the activity of protoporphyrin IX (PpIX) biosynthesis in the GSLCs and the parental A172 glioma cells, we examined the expression levels of biosynthesis enzymes and transporters for PpIX using qRT-PCR, and investigated the intracellular levels of PpIX with use of flow cytometry analysis. Then, we evaluated the sensitivity of these cells to ALA-PDT in vitro. Finally, to confirm the therapeutic impact of ALA-PDT on GSLCs with more clinically relevant model, we performed the same experiment using three different patient-derived glioma sphere lines, which cultivated them either in stem cell media or under differentiation conditions in the presence of serum. RESULTS AND CONCLUSION: GSLCs expressed higher mRNA levels of PpIX biosynthesis enzymes and its transporters PEPT1/2 and ABCB6, when compared to the parental A172 glioma cells. Consistently, flow cytometry analysis revealed that upon incubation with ALA, GSLCs accumulate a higher level of PpIX. Finally, we showed that GSLCs were more sensitive to ALA-PDT than the original A172 cells, and confirmed that all patient-derived glioma sphere lines also showed significantly increased sensitivity to ALA-PDT if cultivated under the pro-stem cell condition. Our data indicate that ALA-PDT has potential as a novel clinically useful treatment that might eliminate GBM stem cells that are highly resistant to current chemo- and radio-therapy.