Elevated expression of protease-activated receptor 1 via ΔNp63 down-regulation contributes to nodal metastasis in oral squamous cell carcinoma.

Protease-activated receptor 1 (PAR1) is known as a thrombin receptor. Recent studies have reported PAR1 expression in various malignancies; however, its role in oral squamous cell carcinoma (OSCC) requires clarification. A previous study showed that down-regulation of ΔNp63, a homolog of p53, augments PAR1 expression in OSCC. In the present study, the association of PAR1 expression with clinicopathological findings in OSCC was examined retrospectively. Expression of PAR1, thrombin, and ΔNp63 was examined immunohistochemically in OSCC specimens. Patients were divided into three groups based on the expression pattern of PAR1 at the invasive front: group A, PAR1-negative in both cancer and stromal cells; group B, positive in stromal cells but negative in cancer cells; group C, positive in both cancer and stromal cells. Histologically high-grade tumours were significantly more common in group C. Patients in group C had the highest incidence rate of nodal metastasis (P<0.001) and a lower survival rate (P=0.085) than those in the other groups. At the invasive front, in group C, thrombin was expressed but ΔNp63 expression was weak. These results indicate that increased PAR1 expression in both cancer and stromal cells could be a useful predictive marker of nodal metastasis and that ΔNp63 is involved in regulating PAR1 expression.

A clinical investigation of the association between perioperative oral management and prognostic nutritional index in patients with digestive and urinary cancers.

Background: The prognostic nutritional index (pni) is a simple metric calculated using serum albumin and the peripheral lymphocyte count. It was reported that a low pni score is significantly associated with major postoperative complications and poor prognosis. The purpose of the present study was to investigate the effects of perioperative oral management (pom) on the perioperative pni profiles of patients with digestive system or urinary cancers. Study Design: The medical records of 181 patients with cancer who underwent surgery and for whom a pni could be calculated were retrospectively reviewed. Results: The intervention rate with pom was 34.8%. The median preoperative pni score was 48.25 in all patients with a pom intervention [25% to 75% interquartile range (iqr): 44.38-54.13] and 47.25 in those without an intervention (iqr: 42.0-53.5). Compared with patients not receiving pom, those who received pom had significantly higher pni scores from the early postoperative period (p < 0.05). Notably, of patients who could resume oral intake within 3 days after surgery, those who received pom intervention, compared with those who did not, had significantly higher pni scores from the early postoperative period (p < 0.05). Conclusions: Perioperative oral management interventions might have positive effects on the postoperative pni scores of patients with cancer.

Salvage surgery for a locally persistent or recurrent tumour in maxillary cancer patients who have undergone radiotherapy and concomitant intra-arterial cisplatin: implications for surgical margin assessment.

Limited information about salvage surgery is available for locally persistent and recurrent maxillary sinus cancers after the completion of chemoradiation therapy. Seventy-six maxillary sinus cancer patients who had undergone chemoradioselection using initial radiotherapy and concomitant intra-arterial cisplatin were screened retrospectively. Twenty-four of these patients who had a locally persistent or recurrent tumour were investigated. The 2-year overall survival rate of patients with maxillary sinus cancer of all types was 39.0% for those who underwent salvage surgery and 10.0% for those who did not. The 2-year overall survival rate of patients with maxillary sinus squamous cell carcinoma was 45.8% for those who underwent salvage surgery and 11.1% for those who did not. Furthermore, the 2-year local control and overall survival rates of patients with positive and negative surgical margins were 14.3% and 83.3% and 14.3% and 66.7%, respectively. There were significant differences in local control (P=0.004) and overall survival (P=0.005) regarding surgical margin status. Although salvage surgery for a locally persistent or recurrent maxillary sinus cancer is a feasible treatment, patients with positive surgical margins are more prone to local relapse. Therefore, surgical safety margins should be assessed thoroughly.

Proposal of patient-specific growth plate cartilage xenograft model for FGFR3 chondrodysplasia.

OBJECTIVE: FGFR3 chondrodysplasia is caused by a gain-of-function mutation of the FGFR3 gene. The disease causes abnormal growth plate cartilage and lacks effective drug treatment. We sought to establish an in vivo model for the study of FGFR3 chondrodysplasia pathology and drug testing. DESIGN: We created cartilage from human induced pluripotent stem cells (hiPSCs) and transplanted the cartilage into the subcutaneous spaces of immunodeficient mice. We then created cartilage from the hiPSCs of patients with FGFR3 chondrodysplasia and transplanted them into immunodeficient mice. We treated some mice with a FGFR inhibitor after the transplantation. RESULTS: Xenografting the hiPSC-derived cartilage reproduced human growth plate cartilage consisting of zones of resting, proliferating, prehypertrophic and hypertrophic chondrocytes and bone in immunodeficient mice. Immunohistochemistry of xenografts using anti-human nuclear antigen antibody indicated that all chondrocytes in growth plate cartilage were human, whereas bone was composed of human and mouse cells. The pathology of small hypertrophic chondrocytes due to up-regulated FGFR3 signaling in FGFR3 skeletal dysplasia was recapitulated in growth plate cartilage formed in the xenografts of patient-specific hiPSC-derived cartilage. The mean diameters of hypertrophic chondrocytes between wild type and thanatophoric dysplasia were significantly different (95% CI: 13.2-26.9; n = 4 mice, one-way analysis of variance (ANOVA)). The pathology was corrected by systemic administration of a FGFR inhibitor to the mice. CONCLUSION: The patient-specific growth plate cartilage xenograft model for FGFR3 skeletal dysplasia indicated recapitulation of pathology and effectiveness of a FGFR inhibitor for treatment and warrants more study for its usefulness to study disease pathology and drug testing.

Regression of gastric de novo diffuse large B-cell lymphoma following Helicobacter pylori eradication: a case report.

We report a case of primary gastric diffuse large B-cell lymphoma (DLBCL), de novo DLBCL without the features of mucosa-associated lymphoid tissue (MALT) lymphoma, which regressed after Helicobacter pylori (HP) eradication. A 27-year-old Japanese female with epigastralgia was revealed to have ulcerated lesions in the angle and antral regions on gastroscopy. Biopsy specimen was consistent with a diagnosis of DLBCL without MALT lymphoma component, indicating de novo development. Her clinical staging on the Lugano system was Stage I. HP was positive on a rapid urease test, and she received HP eradication therapy twice, because the first therapy was not successful. On gastroscopy performed 1 month after the second HP eradication therapy, no ulcerated lesion was noted, and the lymphoma cells had regressed histopathologically. (Acta gastro-enterol. belg., 2016, 79, 367-369A).

Evaluation of brain and head and neck tumors with 4D contrast-enhanced MR angiography at 3T.

BACKGROUND AND PURPOSE: Systematic assessment of brain and head and neck tumors with 4D-CE-MRA at 3T has not been investigated. The purpose of this study was to test the hypothesis that 4D-CE-MRA at 3T can replace DSA in the identification of feeding arteries and tumor stain to plan interventional procedures in hypervascular brain and head and neck tumors. MATERIALS AND METHODS: Fifteen consecutive patients with brain and head and neck tumors underwent 4D-CE-MRA at 3T and DSA. 4D-CE-MRA combined randomly segmented central k-space ordering, keyhole imaging, SENSE, and half-Fourier imaging. We obtained 30 dynamic scans every 1.9 seconds at an acquired spatial resolution of 0.9 × 0.9 × 1.5 mm; the matrix was 256 × 256. Two independent observers inspected the 4D-CE-MRA images for the main arterial feeders and tumor stain. Interobserver and intermodality agreement was assessed by κ statistics. RESULTS: For 4D-CE-MRA, the interobserver agreement was fair with respect to the main arterial feeders and very good for the degree of tumor stain (κ = 0.28 and 0.87, respectively). Intermodality agreement was moderate for the main arterial feeders (κ = 0.45) and good for the tumor stain (κ = 0.74). CONCLUSIONS: Although 4D-CE-MRA may be useful for evaluating tumor stain in hypervascular brain and head and neck tumors, it is not able to replace DSA in planning interventional procedures.

Quantitative blood flow measurements in gliomas using arterial spin-labeling at 3T: intermodality agreement and inter- and intraobserver reproducibility study.

BACKGROUND AND PURPOSE: QUASAR is a particular application of the ASL method and facilitates the user-independent quantification of brain perfusion. The purpose of this study was to assess the intermodality agreement of TBF measurements obtained with ASL and DSC MR imaging and the inter- and intraobserver reproducibility of glioma TBF measurements acquired by ASL at 3T. MATERIALS AND METHODS: Two observers independently measured TBF in 24 patients with histologically proved glioma. ASL MR imaging with QUASAR and DSC MR imaging were performed on 3T scanners. The observers placed 5 regions of interest in the solid tumor on rCBF maps derived from ASL and DSC MR images and 1 region of interest in the contralateral brain and recorded the measured values. Maximum and average sTBF values were calculated. Intermodality and intra- and interobsever agreement were determined by using 95% Bland-Altman limits of agreement and ICCs. RESULTS: The intermodality agreement for maximum sTBF was good to excellent on DSC and ASL images; ICCs ranged from 0.718 to 0.884. The 95% limits of agreement ranged from 59.2% to 65.4% of the mean. ICCs for intra- and interobserver agreement for maximum sTBF ranged from 0.843 to 0.850 and from 0.626 to 0.665, respectively. The reproducibility of maximum sTBF measurements obtained by methods was similar. CONCLUSIONS: In the evaluation of sTBF in gliomas, ASL with QUASAR at 3T yielded measurements and reproducibility similar to those of DSC perfusion MR imaging.

Assessment of vascular supply of hypervascular extra-axial brain tumors with 3T MR regional perfusion imaging.

BACKGROUND AND PURPOSE: The vascular supply of extra-axial brain tumors provided by the external carotid artery has not been studied with RPI. The purpose of this work was to determine whether RPI assessment is feasible and provides information on the vascular supply of hypervascular extra-axial brain tumors. MATERIALS AND METHODS: Conventional ASL and RPI studies were performed at 3T in 8 consecutive patients with meningioma. On the basis of MRA results, we performed RPI by placing a selective labeling slab over the external carotid artery. Five patients underwent DSA before surgery. Two neuroradiologists independently evaluated the overall image quality, the degree of tumor perfusion, and the extent of the tumor vascular territory on conventional ASL and RPI. RESULTS: In overall quality of conventional ASL and RPI, no images interfered with interpretation. In comparisons of the vascular tumor territory identified by the conventional ASL and RPI techniques, the territories coincided in 3 cases, were partially different in 4, and completely different in 1. The interobserver agreement was very good (kappa = 0.82). In 5 patients who underwent DSA, the 4 patients in whom the dominant supply was the external carotid artery were scored as coincided or partially different. The 1 patient in whom the vascular supply was from the internal carotid artery was scored as completely different. CONCLUSIONS: RPI with selective labeling of the external carotid artery is feasible and may provide information about the vascular supply of hypervascular extra-axial brain tumors.

Cost benefit and clinical efficacy of low-dose granulocyte colony-stimulating factor after standard chemotherapy in patients with non-Hodgkin's lymphoma.

High costs of molecule-targeted drugs, such as rituximab, ibritumomab, and tositumomab have given rise to an economical issue for treating patients with non-Hodgkin's lymphoma (NHL). Granulocyte colony-stimulating factors (G-CSFs), which are also expensive, are widely used for treating neutropenia after chemotherapy. In Japan, lenograstim at 2 microg/kg (about 100 microg/body) or filgrastim at 50 microg/m(2) (about 75 microg/body) is commonly administered for patients with NHL after chemotherapy. Therefore, cost-effectiveness is an important issue in treatment for NHL. Patients with advanced-stage NHL who needed chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or a CHOP-like regimen with or without rituximab were enrolled in this randomized cross-over trial to investigate the efficacy and safety of low-dose G-CSF. Half of the patients were administered 75 microg filgrastim in the first course after neutropenia and 50 microg lenograstim in the second course, and the other half were crossed over. Forty-seven patients were enrolled in this cross-over trial, and 24 patients completed the trial. Frequencies and durations of grade 4 leukocytopenia and neutropenia were similar in the two groups. Severe infection was rare and was observed at similar frequency. Frequencies of antibiotics use were also similar. The total cost of G-CSF (cost/drug x duration of administration) was significantly lower in patients who received 50 microg lenograstim. Hence, a low dose of lenograstim might be safe, effective and pharmaco-economically beneficial in patients with advanced-stage NHL.

Differentiation between paraclinoid and cavernous sinus aneurysms with contrast-enhanced 3D constructive interference in steady- state MR imaging.

BACKGROUND AND PURPOSE: Differentiation between paraclinoid and cavernous sinus aneurysms of the internal carotid artery (ICA) is critical when considering treatment options. The purpose of this study was to determine whether contrast-enhanced (CE) 3D constructive interference in steady state (CISS) MR imaging is useful to differentiate between paraclinoid and cavernous sinus aneurysms. MATERIALS AND METHODS: This study included 11 aneurysms in 10 consecutive female patients, ranging from 52 to 66 years of age. All aneurysms were adjacent to the anterior clinoid process. After conventional and CE 3D-CISS imaging on a 1.5T MR imaging unit, all patients underwent surgery, and the relationship between the aneurysms and the dura was confirmed. Two neuroradiologists evaluated the location of the aneurysms on CE 3D-CISS images and classified them as intradural, partially intradural, and extradural aneurysms. Operative findings were used as a reference standard. To understand the imaging characteristics, we assessed the boundary and signal intensity of the cavernous sinus, CSF, and carotid artery on the side contralateral to the lesion. RESULTS: Operative findings disclosed that 5 aneurysms were intradural and 6 were extradural. All except 2 were accurately assessed with CE 3D-CISS imaging. One intradural aneurysm adjacent to a large cavernous aneurysm and 1 cavernous giant aneurysm were assessed as partially intradural. On CE 3D-CISS images, the boundary between the CSF, cavernous sinus, and carotid artery was identified by high signal-intensity contrast in all cases. CONCLUSION: CE 3D-CISS MR imaging is useful for the differentiation between paraclinoid and cavernous sinus aneurysms.

Clinical evaluation of cellulose porous beads for the therapeutic embolization of meningiomas.

BACKGROUND AND PURPOSE: Cellulose porous beads (CPBs) are a new, exceptionally uniformly sized, nonabsorbable embolic agent. We evaluated their efficacy in the preoperative embolization of meningiomas. METHODS: In 141 consecutive patients, we used CPBs (200-microm diameter) for the preoperative embolization of meningiomas. We selected patients whose tumors were > or =4 cm with 50% of blood to the tumor supplied by the external carotid artery (ECA). All patients underwent a provocation test before embolization. The percentage of blood supplied to the tumor by the internal carotid artery and ECA was determined angiographically. Nonenhanced areas on postembolization MR imaging were calculated. Intraoperative blood loss, units of blood transfusion, and hemostasis at the time of surgery were recorded for each patient. The interval between embolization and surgery was intentionally longer than 7 days. RESULTS: Of the 141 patients, 128 underwent CBP embolization. Eleven patients had positive provocation test results, and 2 had vasospasm; they were not CBP embolized. In 72% of the patients CBP embolization achieved reduction in the flow of the feeding artery by more than 50%. The nonenhanced area on MR imaging was not significantly correlated with the degree of ECA supply or devascularization. The interval between embolization and surgery was 8-26 days (mean, 9.9 days). The longer this interval, the greater was the tumor-softening effect and the rate of tumor removal. CONCLUSIONS: CPBs may be useful for the preoperative embolization of meningiomas. To increase the efficacy of CPB embolization, the interval to surgery should be at least 7 days.

Evaluation of the Stability of Small Ruptured Aneurysms with a Small Neck after Embolization with Guglielmi Detachable Coils. Correlation between Coil Packing Ratio and Coil Compaction.

SUMMARY: It is difficult to predict the compaction of Guglielmi detachable coils (GDC) after endovascular surgery for aneurysms. Therefore, we studied the relationship between the coil packing ratio and compaction in 62 patients with acute ruptured intracranial aneurysms that were small (< 10 mm) had a small neck (< 4 mm) and were coil-embolized with GDC-10. We recorded the maximum prospective coil length, L, as the length that correspond with the volume of packed coils occupying 30% of the aneurysmal volume. L was calculated as L (cm) = 0.3 x a x b x c and the coil packing ratio expressed as packed coil length/L x 100, where a, b, and c are the aneurysmal height, length, and width in mm, respectively. Angiographic followup studies were performed at three months and one and two years after endovascular surgery. Of the 62 patients, 16 (25.8%) manifested angiographic coil compaction (ten minor and six major compactions); the mean coil packing ratio was 51.9 +/- 13.4%. The mean coil packing ratio in the other 46 patients was 80.5 +/- 20.2% and the difference was statistically significant (p < 0.01). In all six patients with major compaction the mean packing ratio was below 50%. We detected 93.8% of the compactions within 24 months of coil placement. In patients with small, necked aneurysms, the optimal coil packing ratio could be identified with the formula 0.3 x a x b x c. The probability of compaction was significantly higher when the coil packing ratio was under 50%. To detect coil compaction post-embolization, follow-up angiograms must be examined regularly for at least 24 months.

A nonadhesive liquid embolic agent of ethylene vinyl alcohol copolymer and ethanol mixture for cerebral arteriovenous malformations. Clinical experience.

SUMMARY: We report our experience using our new nonadhesive liquid embolic agent, an ethylene vinyl alcohol copolymer (EVAL)/Ethanol mixture, to treat human arteriovenous malformations (AVM). Between June 1995 and April 2001, 57 patients with confirmed AVM underwent embolization with the EVAL/Ethanol mixture. Using 87 procedures consisting of one to three stages, we embolized 185 feeding arteries to occlude as much of the AVM as possible. Repeated injections under fluoroscopic control could be performed smoothly without encountering cementing of the catheter in the vessel wall. Among 87 procedures undertaken in 57 patients, seven (8.0%) procedures in six patients produced new postembolization symptoms. Resolution of these symptoms occurred within hours or days following four of the seven procedures; permanent neurological deficits remained after three embolization procedures (3.4%). Of the 57 patients, three underwent postembolization radiosurgery, 54 were radically treated with microsurgical extirpation. Histopathological examinations of the 54 specimens disclosed mild inflammation within the embolized lumen without inflammatory reactions in the media or adventitia. Follow-up angiograms obtained three years after they underwent radiosurgery showed that in all three patients the nidus had completely disappeared. The EVAL/Ethanol mixture is handled easily and appears to be an effective and safe embolic agent for the preoperative embolization of AVM.

Brain stem venous congestion due to dural arteriovenous fistulas of the cavernous sinus.

BACKGROUND: Venous congestion of the brain stem due to dural arteriovenous fistulas (DAVFs) in the cavernous sinus is rare and presents therapeutic challenges. To assess the prognosis of patients with symptomatic DAVFs and brain stem dysfunction, we evaluated the degree of venous ischemia by examining pre- and post-treatment magnetic resonance images (MRI) in 2 patients presenting with venous congestion of the brain stem. METHODS: A 56-year-old woman with left hemiparesis and a 70-year-old woman with gait disturbance attributable to right cavernous sinus DAVFs were referred to our hospital. In both cases, T2-weighted magnetic resonance imaging (MRI) disclosed a hyperintensity lesion in the brainstem due to venous congestion. FINDINGS: Both patients underwent open surgery for direct embolization of the cavernous sinus because there were no approach routes for transvenous embolization. The patient whose pretreatment MRI demonstrated Gd enhancement continued to manifest neurological deficits and persistence of the abnormal hyperintensity on post-treatment T2-weighted MRI. In the other patient whose pretreatment MRI showed no Gd enhancement, treatment produced a complete response of her neurological deficit and disappearance of the abnormal hyperintensity area. CONCLUSIONS: We tentatively conclude that lesions corresponding to hyperintensity areas on non-Gd-enhanced, T2-weighted MRI may reflect a reversible condition whereas lesions identified as hyperintense areas on GD-enhanced T2-weighted MRI may be indicative of irreversibility.

Endovascular coil trapping for ruptured vertebral artery dissecting aneurysms by using double microcatheters technique in the acute stage.

BACKGROUND: In the treatment of vertebral artery (VA) dissecting aneurysms, only proximal occlusion of the VA does not necessarily prevent rerupture. We evaluated the efficacy of coil trapping for the ruptured VA dissecting aneurysms using the double microcatheters technique. METHODS: We treated 11 patients who presented with subarachnoid haemorrhage (SAH) due to rupture of a VA dissecting aneurysm which did not involve the posterior inferior cerebellar artery at the site of dissection. All patients tolerated the balloon occlusion test. Within 3 days of the SAH, the dissection site was trapped with a Guglielmi detachable coil (GDC) using the double microcatheters technique. The proximal and distal sites of the dissecting aneurysm were embolized simultaneously. FINDINGS: GDC trapping at the affected site was successful in all 11 patients. Radiographic findings showed complete occlusion of the dissection site and patency of the unaffected artery. Although one patient experienced transient dysphagia, there were no major complications. INTERPRETATION: The double microcatheters technique is effective for coil trapping of ruptured VA dissecting aneurysms in selected patients. The risks posed by this simple technique are minimal, even in the acute stage.

Neuroprotective effect of sodium orthovanadate on delayed neuronal death after transient forebrain ischemia in gerbil hippocampus.

In transient forebrain ischemia, sodium orthovanadate as well as insulinlike growth factor-1 (IGF-1) rescued cells from delayed neuronal death in the hippocampal CA1 region. Adult Mongolian gerbils were subjected to 5-minute forebrain ischemia. Immunoblotting analysis with anti-phospho-Akt/PKB (Akt) antibody showed that phosphorylation of Akt at serine-473 (Akt-Ser-473) in the CA1 region decreased immediately after reperfusion, and in turn transiently increased 6 hours after reperfusion. The decreased phosphorylation of Akt-Ser-473 was not observed in the CA3 region. The authors then tested effects of intraventricular injection of orthovanadate and IGF-1, which are known to activate Akt. Treatment with orthovanadate or IGF-1 30 minutes before ischemia blocked delayed neuronal death in the CA1 region. The neuroprotective effects of orthovanadate and IGF-1 were associated with preventing decreased Akt-Ser-473 phosphorylation in the CA1 region observed immediately after reperfusion. Immunohistochemical studies with the anti-phospho-Akt-Ser-473 antibody also demonstrated that Akt was predominantly in the nucleus and was moderately activated in the cell bodies and dendrites of pyramidal neurons after orthovanadate treatment. The orthovanadate treatment also prevented the decrease in phosphorylation of mitogen-activated protein kinase (MAPK). Pretreatment with combined blockade of phosphatidylinositol 3-kinase and MAPK pathways totally abolished the orthovanadate-induced neuroprotective effect. These results suggest that the activation of both Akt and MAPK activities underlie the neuroprotective effects of orthovanadate on the delayed neuronal death in the CA1 region after transient forebrain ischemia.

[Treatment of spontaneous carotid-cavernous fistula by the transvenous approach via the facial and angular route].

We report a case of a patient with a spontaneous carotid-cavernous sinus fistula (CCF) who was successfully treated by the facial vein approach. This 66-year-old female had a 3-month history of right chemosis and exophthalmos. Angiograms showed a spontaneous right CCF with primary drainage via the superior ophthalmic vein. As both inferior petrosal sinuses were hypoplastic, the transvenous approach could not be used to gain access to the right cavernous sinus. With effort, we were able to traverse the sharp angle at the corner of the angular vein and the superior ophthalmic vein with a microcatheter. Thereafter, it was easily navigated into the right cavernous sinus. Successful placement of Guglielmi detachable coils resulted in complete closure of the fistula. When it is difficult to gain access to the cavernous sinus via the inferior petrosal sinus, the facial vein approach is a useful alternative.

Expression of angiopoietin-2 in human glioma cells and its role for angiogenesis.

In highly vascular malignant glioma, glioma cells themselves may express angiogenic factors and induce angiogenesis. Recent studies have shown that novel angiogenic factors, angiopoietin-1 (Ang1) and -2 (Ang2), play important roles in the modulation of vasculogenesis and angiogenesis. In this study, we determined Ang2 mRNA expression in cultured human malignant glioma cells (U105, U251, and U373 MG) by reverse transcriptase-PCR. Western blot analysis and immunocytochemical analysis with antihuman Ang2 antibody revealed that Ang2 protein was expressed and secreted by these cells. Furthermore, hypoxia increased the Ang2 protein level in cultured glioma cells. Serial sections of 32 human glioma tissues (14 glioblastomas, eight anaplastic astrocytomas, seven astrocytomas, and three pilocytic astrocytomas) were immunostained against Ang2, vascular endothelial growth factor, Tie2, von Willebrand factor, and alpha smooth muscle actin. The immunoreactivity of each angiogenic factor was higher in malignant gliomas than in low-grade gliomas. Ang2 protein was detected not only in endothelial cells but also in glioma cells, and its expression was prominent in both the area surrounding the necrosis and the periphery of glioblastomas. In the area surrounding necrosis, Ang2 was highly expressed and tumor vessels showed regression. In the tumor periphery, Ang2 was highly expressed and many small vessels stained positively for von Willebrand factor but not for alpha smooth muscle actin, suggesting angiogenesis. Statistical analysis revealed that the Ang2 expression was negatively correlated with vessel maturation in malignant gliomas and that vascular endothelial growth factor expression was positively correlated with vessel maturation in low-grade gliomas (P < 0.05). These results suggest that glioma cells themselves express Ang2 and that expression may be induced by hypoxic stimulation and may play a crucial role in the vessel maturation, angiogenesis, and vessel regression in malignant glioma.

Prognostic factors for survival and bladder recurrence in transitional cell carcinoma of the upper urinary tract.

BACKGROUND: Prognostic factors for survival in transitional cell carcinoma of the upper urinary tract have been extensively evaluated, but detailed analyses of patterns of bladder recurrence after surgery have been rare. METHODS: The outcome and tumor recurrence of 93 patients with transitional cell carcinoma of the upper urinary tract surgically treated between 1975 and 1999 were reviewed, retrospectively. Disease-specific survival by pathologic stage and grade were analyzed by the Kaplan-Meier METHOD: Prognostic factors for survival and bladder recurrence were examined by univariate and multivariate analysis. RESULTS: The 5-year disease-specific survival rates of the patients with pTa, T1 and T2 were 92.9%, 100% and 88.9%, respectively. However, that of the pT3 patients was 61.9% and the median survival of the pT4 cases was only 7 months. Bladder recurrence was seen in 40 cases and recurrences occurred within 1 year in 32 of these patients. The stage and grade of metachronous bladder tumors usually resembled those of primary tumors, but invasive recurrences were seen in 19% of recurrent cases with primary pTa, pT1 tumors. The significant prognostic factor for survival was pathologic stage (pT3, pT4), but no significant variables were detected for bladder recurrence by multivariate analysis. CONCLUSIONS: The prognosis of pT3, pT4 patients is poor and effective systemic adjuvant therapy is necessary. Invasive bladder recurrence occurred in 19% of patients with superficial primary tumors. As no significant prognostic variables for bladder recurrence were identified, careful follow up for bladder recurrence is important even if the primary tumors are non-invasive.