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Purpose: To evaluate the biologic efficacy of intravitreal bevacizumab (IVB) for iris neovascularization (INV) or neovascular glaucoma (NVG) in patients with ischemic retinal disorders., Design: Retrospective, consecutive, interventional case series., Participants: Thirty patients (41 eyes) with INV or NVG secondary to ischemic retinal disorders., Methods: Patients received IVB (1 mg) as the initial treatment for INV or NVG and were followed up for at least 6 months. Ophthalmic evaluations included measurement of visual acuity and intraocular pressure (IOP), a complete ophthalmic examination, and fluorescein angiography. Patients were divided into 3 subgroups: INV without elevated IOP (INV group), NVG with an open angle (O-NVG group), and NVG with angle closure (C-NVG group) for outcomes analysis., Main Outcome Measures: The controllability of IOP by IVB, incidence of recurrence, and requirement for surgery to treat NVG., Results: No significant ocular or systemic adverse events developed during follow-up (range, 6-22 months; mean, 13.3 months). The mean IOP levels were 14.7, 31.2, and 44.9 mmHg at baseline in the INV, O-NVG, and C-NVG groups, respectively. In the INV group (9 eyes), the INV regressed or resolved after 1 injection. Iris neovascularization recurred in 4 eyes by 6 months and stabilized after repeated injections without IOP elevation. In the O-NVG group (17 eyes), rapid neovascular regression with successful IOP normalization (

Objectives: This study was designed to evaluate contrast-enhanced ultrasound imaging of carotid atherosclerosis as a clinical tool to study intraplaque neovascularization., Background: Plaque neovascularization is associated with plaque vulnerability and symptomatic disease; therefore, imaging of neovascularization in carotid atherosclerosis may represent a useful tool for clinical risk stratification and monitoring the efficacy of antiatherosclerotic therapies., Methods: Thirty-two patients with 52 carotid plaques were studied by standard and contrast-enhanced ultrasound imaging. In 17 of these patients who underwent endarterectomy, the surgical specimen was available for histological determination of microvessel density by CD31/CD34 double staining. Plaque echogenicity and degree of stenosis at standard ultrasound imaging were evaluated for each lesion. Contrast-agent enhancement within the plaque was categorized as absent/peripheral (grade 1) and extensive/internal (grade 2)., Results: In the surgical subgroup, plaques with higher contrast-agent enhancement showed a greater neovascularization at histology (grade 2 vs. grade 1 contrast-agent enhancement: median vasa vasorum density: 3.24/mm(2) vs. 1.82/mm(2), respectively, p = 0.005). In the whole series of 52 lesions, echolucent plaques showed a higher degree of contrast-agent enhancement (p < 0.001). Stenosis degree was not associated with neovascularization at histology or with the grade of contrast-agent enhancement., Conclusions: Carotid plaque contrast-agent enhancement with sonographic agents correlates with histological density of neovessels and is associated with plaque echolucency, a well-accepted marker of high risk lesions, but it is unrelated to the degree of stenosis. Contrast-enhanced carotid ultrasound imaging may provide valuable information for plaque risk stratification and for assessing the response to antiatherosclerotic therapies, beyond that provided by standard ultrasound imaging.

Background: Saphenofemoral junction (SFJ) ligation has been a major component of surgical intervention for varicose veins; however, recurrence occurs in as many as 40%. Neovascularization with reconnection of the venous channels at the transected SFJ has been identified as the major cause of this recurrence. This randomized controlled study sought to evaluate mechanical suppression of neovascularization at the SFJ, with the use of a synthetic patch, to prevent recurrence after ligation surgery., Methods and Results: A total of 389 limbs (from 292 patients) were randomized into either control (SFJ ligation surgery) or patch (SFJ ligation with polytetrafluoroethylene patch of the transected SFJ) groups. All patients underwent clinical assessment, duplex imaging, and air plethysmography studies preoperatively and at 1, 6, 12, and 36 months postoperatively. The patch consistently halved the recurrence rate to 3 years postoperatively in all clinical subgroups. In those patched SFJs that still developed recurrence, evidence of neovascularization circumventing the polytetrafluoroethylene patch was observed by both ultrasound and histology., Conclusions: This study demonstrates that use of a polytetrafluoroethylene patch is an effective mechanical suppressant of neovasculogenesis at the SFJ and can be safely used as a strategy to improve long-term outcome of varicose vein surgery.

Purpose: To report the clinical course and outcome of surgery for idiopathic epiretinal membranes (ERMs) centered on retinal blood vessels., Methods: Retrospective observational case series review of the case records of 15 patients with idiopathic ERMs overlying retinal blood vessels, of whom 9 underwent vitrectomy with membrane peeling. The patients attended two eye departments under the care of four vitreoretinal surgeons with a total of more than 50 years of surgical experience., Results: The patients were aged 12-74 years (mean = 34.3 years). Difficulties were experienced in achieving vitreoretinal and membranoretinal separation in the 9 eyes undergoing vitreous microsurgery. Recurrent ERM formation occurred in 8 of these eyes (89%) of which 6 underwent revision vitrectomy. Visual improvement was achieved in 55% of patients. Mean follow-up was 2.5 years., Conclusions: The authors describe a subgroup of patients with idiopathic ERMs in which the membrane is centered over a large retinal vessel. This occurs predominantly but not exclusively in a young age group. Surgical removal is characterized by a high recurrence rate.

Background and Aim: Hepatocellular carcinoma is one of the most common cancers. alpha-Fetoprotein is strongly expressed in most patients with hepatocellular carcinoma, and high levels of alpha-fetoprotein expression have been reported as an independent prognostic factor. However, there have been few reports on the reasons for poor prognosis., Methods: We analyzed the correlation between serum alpha-fetoprotein levels and clinicopathological findings in 37 hepatocellular carcinoma patients undergoing curative surgery. alpha-Fetoprotein mRNA expression in tissue samples was analyzed by quantitative reverse transcription-polymerase chain reaction (RT-PCR), while protein expression was assessed by immunohistochemistry. To assess the mechanistic correlations between alpha-fetoprotein and tumor progression, we further analyzed cell proliferation (Ki-67), angiogenesis (CD34), and apoptosis (TdT-mediated dUTP-biotin nick end labeling [TUNEL] assay)., Results: Post-operative serum alpha-fetoprotein levels were correlated with disease-free and overall survival, and were an independent prognostic factor for survival. alpha-Fetoprotein expression, as assessed by immunohistochemistry, was strong and heterogeneous in hepatocellular carcinoma. Control livers did not express alpha-fetoprotein and there was weak expression of alpha-fetoprotein in adjacent regions in hepatocellular carcinoma patients. The Ki-67 labeling index in the high serum alpha-fetoprotein cases was significantly higher than in alpha-fetoprotein-negative cases (P = 0.042). The alpha-fetoprotein-positive cases also showed a significantly higher microvessel density than alpha-fetoprotein-negative cases (P = 0.035), whereas hepatocellular carcinoma without alpha-fetoprotein overexpression had a higher apoptotic index when compared to hepatocellular carcinoma with alpha-fetoprotein overexpression (P = 0.033)., Conclusion: These results indicate that the poor prognosis associated with high alpha-fetoprotein is due to high cell proliferation, high angiogenesis, and low apoptosis.

Unlabelled: PURPOSE AND MATERIALS: Punctate inner choroidopathy (PIC), first described by Watzke et al(1), is a disease in young women of child-bearing age. We present three cases of PIC-associated choroidal neovascular membrane (CNVM) occurring during pregnancy, and discuss associated investigative and treatment dilemmas., Results: All three patients described showed evidence of recurrence of CNVM during their pregnancy. None underwent FFA but benefited from OCT monitoring. Different therapeutic strategies were adopted in each of our cases. Case 1, with a history of spontaneous CNVM regression, was managed conservatively. Cases 2 and 3 chose steroid treatment to their better-seeing eye. All cases remained stable postpartum., Discussion: Management of PIC-related CNVM creates diagnostic and therapeutic challenges. The problem is exacerbated as the pathology is often sequentially bilateral and sight threatening. Owing to the rarity of such cases, there is a paucity of evidence on which to base the treatment strategies. A history of pregnancy should always be elicited before investigation with FFA, and women warned of the potential for disease exacerbation with limited therapeutic options during pregnancy., Conclusions: spontaneous resolution of CNVM is common in PIC, and should be borne in mind while treating pregnant women. Peri/intraocular steroid injection represents a reasonable option for sight-threatening CNVM in the better-seeing eye.

To investigate the anti-inflammatory and anti-angiogenic effects of mesenchymal stem cells (MSC) in the chemically burned corneas, we mechanically removed the corneal epithelium of rats after 100% alcohol instillation. The rats were then randomized into four groups: fresh media, conditioned media derived from the MSC culture (MSC-CM), MSC applied topically to the damaged corneas for 2 hours immediately after the injury or MSC-CM applied either once or 3 times per day for 3 consecutive days. Corneal surface was evaluated every week. After 3 weeks, the corneas were stained with the hematoxylin-eosin, and the expression of interleukin (IL)-2, interferon (IFN)-gamma, IL-6, IL-10, transforming growth factor (TGF)-beta1, thrombospondin-1 (TSP-1), matrix metalloproteinase-2 (MMP-2), and vascular endothelial growth factor (VEGF) were analyzed. CD4+ cells were assessed in the corneas. We found that both MSC and three-time applied MSC-CM (1) reduced corneal inflammation and neovascularization, (2) decreased IL-2 and IFN-gamma, although increased IL-10 and TGF-beta1 as well as IL-6, (3) reduced the infiltration of CD4+ cells, and (4) upregulated the expression of TSP-1, although downregulated that of MMP-2. Interestingly, whereas three-time application of MSC-CM was partially effective, transplantation of MSC achieved a better outcome in suppressing corneal inflammation. The results of this study suggest that the anti-inflammatory and anti-angiogenic action of MSC in the chemically burned corneas might be mediated in part through paracrine pathways involving soluble factors such as IL-10, TGF-beta1, IL-6 and TSP-1.

Background: Angiogenesis has been shown to be increased in various human tumors including head and neck squamous cell carcinoma (SCC). Vascular endothelial growth factor (VEGF) is thought to be one of the most important angiogenic factors in tumorigenesis. In this study, we aimed to investigate whether polymorphism of VEGF-1154 (A/G) genotypes are associated with the risk of laryngeal SCC., Methods: A prospective, randomized, case-control study in a tertiary university hospital was done. The study group consisted of 57 Caucasian patients with laryngeal SCC and 89 control subjects. Blood samples were obtained before surgery or from the patients under follow-up to 5 years after surgery. VEGF-1154 (A/G) genotypes were detected by real-time polymerase chain reaction with thermal cycler system., Results: According to the high-risk (GG) genotype, the difference between the patient and control groups was statistically significant (OR 0.43, 95% CI=0.19-0.95, p=0.037)., Conclusions: GG genotype of the VEGF gene may increase the risk of laryngeal SCC in this population. VEGF gene polymorphism may be an important potential genetic and therapeutic marker of laryngeal SCC.

Familial exudative vitreoretinopathy (FEVR) is a well-defined inherited disorder of retinal vessel development. Association of FEVR with other congenital ocular diseases has already been described. We report the first clinical case of FEVR associated with hyaloid artery persistence. An 18-year-old Tunisian woman and four members of her family (mother, two brothers, and sister) presented signs of FEVR. Examination of this patient also revealed functional hyaloid artery persistence in her right eye. These two disorders have many common aspects in their pathological process, in particular vascular endothelial growth factor expression, which can explain this association.

The aim of the present study was to monitor photodynamic angioocclusion with verteporfin in capillaries. Details of this process were recorded under a microscope in real-time using a high-sensitivity video camera. A procedure was developed based on intravenous (i.v.) injection of a light-activated drug, Visudyne, into the chorioallantoic membrane (CAM) of a 12-day-old chicken embryo. The effect of light activation was probed after 24 h by i.v. injection of a fluorescent dye (FITC dextran), and analysis of its fluorescence distribution. The angioocclusive effect was graded based on the size of the occluded vessels, and these results were compared with clinical observations. The time-resolved thrombus formation taking place in a fraction of the field of view was video recorded using a Peltier-cooled CCD camera. This vessel occlusion in the CAM model was reproducible and, in many ways, similar to that observed in the clinical use of verteporfin. The real-time video recording permitted the monitoring of platelet aggregation and revealed size-selective vascular closure as well as some degree of vasoconstriction. Platelets accumulated at intravascular junctions within seconds after verteporfin light activation, and capillaries were found to be closed 15 min later at the applied conditions. Larger-diameter vessels remained patent. Repetition of these data with a much more sensitive camera revealed occlusion of the treated area after 5 min with doses of verteporfin and light similar to those used clinically. Consequently, newly developed light-activated drugs can now be studied under clinically relevant conditions.

Antiangiogenesis has been exploited as an effective approach to inhibit the growth of solid tumors. This technique has been evaluated using various vectors in several xenograft animal models to demonstrate the efficacy of endostatin gene therapy against cancer growth. However, previous studies have not examined the use of cord blood CD34+ cells as endostatin-producing cells for gene therapy against hepatoma. This exploratory study was done to investigate the local effects of CD34+ cells transduced with the endostatin gene on a mouse xenograft tumor model. The human endostatin gene was transferred into CD34+ cells using the recombinant retrovirus plasmid, pLncx/endo. Expression was verified by RT-PCR and Western blot analyses, confirming the stable expression and secretion of endostatin from the transferred CD34+ cells. The proliferation of vascular endothelial cells was evaluated by MTT assay and found to decrease by about 59.9% when treated with the supernatant of cultured transfected CD34+ cells in vitro. These genetically modified cord blood CD34+ cells were implanted intratumorally and tumor regression was evaluated after 2 weeks. The average size of a xenograft tumor in the CD34+/endo group was reduced 31.39% compared to that in the untreated mice or those transplanted with CD34+ cells transduced with a control vector. The microvascular density of the tumor decreased 62.45% in the treated group. The expression of proliferation cell nuclear antigen (PCNA) also decreased significantly in the treated group. Moreover, the apoptotic index (AI) of tumors, as evaluated by TUNEL staining, was significantly enhanced in the treatment group. Our findings indicate that angiogenesis of the xenograft tumor in mice may be inhibited by local administration of genetically modified CD34+ cells expressing the endostatin gene. This novel approach may lead to a new direction of cell-based gene therapy for malignancy.

Background: To assess vascular infiltration is crucial in surgical planning of pancreatic cancer. Our aim was to assess the capability of multidetector CT in detecting vascular infiltration., Methods: We evaluated 37 patients with pancreatic tumors. The relation between tumor and vessels was classified: grade 0: no contact between lesion and vessel; grade I: focal contiguity without modification of the vessel caliber; grade II: lesion surrounding the vessel, without reduction of its lumen; grade III: cancer surrounding the vessel with reduction or obstruction of its lumen. CT grades were compared to intraoperative findings and histopathology., Results: We evaluated 52 critical vessels with the following CT grades: grade 0 (4 cases), grade I (13 cases), grade II (17 cases), grade III (18 cases). Vascular resection was performed in 26 patients, with a total of 31 resected vessels (3 of grade 0, 5 of grade I, 8 of grade II, 15 of grade III). Histopathology excluded vascular infiltration in 4/4 cases with grade 0 and in 10/13 cases with grade I and confirmed it in 14/17 cases with grade II and 14/18 cases with grade III., Conclusions: Multidetector CT is accurate in detecting vascular involvement and provides pre-operative information to effectively plan resection.

Introduction: Diffusion-weighted imaging (DWI), perfusion-weighted imaging (PWI) and MR spectroscopy (MRS) provide useful data for tumor evaluation. To assess the contribution of these multimodal techniques in grading glial neoplasms, we compared the value of DWI, PWI and MRS in the evaluation of histologically proven high- and low-grade gliomas in a population of 105 patients., Methods: Independently for each modality, the following variables were used to compare the tumors: minimum apparent diffusion coefficient (ADC) and maximum relative cerebral blood volume (rCBV) normalized values between tumor and healthy tissue, maximum Cho/Cr ratio and minimum NAA/Cr ratio in tumor, and scored lactate and lipid values in tumor. The Mann-Whitney and Wilcoxon tests were employed to compare DWI, PWI and MRS between tumor types. Logistic regression analysis was used to determine which parameters best increased the diagnostic accuracy in terms of sensitivity, specificity, and positive and negative predictive values. ROC curves were determined for parameters with high sensitivity and specificity to identify threshold values to separate high- from low-grade lesions., Results: Statistically significant differences were found for rCBV tumor/normal tissue ratio, and NAA/Cr ratio in tumor and Cho/Cr ratio in tumor between low- and high-grade tumors. The best performing single parameter for group classification was the normalized rCBV value; including all parameters, statistical significance was reached by rCBV tumor/normal tissue ratio, NAA/Cr tumor ratio and lactate. From the ROC curves, a high probability for a neoplasm to be a high-grade lesion was associated with a rCBV tumor/normal tissue ratio of >1.16 and NAA/Cr tumor ratio of <0.44., Conclusion: Combining PWI and MRS with conventional MR imaging increases the accuracy of the attribution of malignancy to glial neoplasms. The best performing parameter was found to be the perfusion level.

A 9-year-old girl presented with a 2-week history of redness in the left eye. Examination revealed vitritis, retinal whitening, vasculitis, and optic nerve head edema. Polymerase chain reaction testing of the aqueous fluid revealed herpes simplex virus type 2. The retinitis was controlled with intravenous acyclovir and intravitreal foscarnet. The clinical course was complicated by retinal neovascularization and vitreous hemorrhage, which was treated by pars plana vitrectomy and endolaser. While there are few case reports of herpes simplex virus type 2 retinitis in children, this one is unique for the following reasons: it is the first reported case of herpes simplex virus type 2 retinitis in a child less than 10 years old without a previous history of neonatal infection or central nervous system involvement; no other children have been reported to have been treated with intravitreal foscarnet; and retinal neovascularization complicated the recovery.

Spontaneous renal rupture is a rare but nevertheless life-threatening complication in cases of benign and malignant space-occupying lesions in the kidneys. A precise preoperative differentiation often turns out to be difficult because of the formation of a hematoma. We report on a 50-year-old female patient with a retroperitoneal hematoma due to a spontaneous renal rupture for which an angiomyolipoma could only by diagnosed after the nephrectomy with histological work-up. In search of the cause, sonography, abdominal computed tomography, and digital subtraction angiography were conducted, which could provide findings suggestive of a space-occupying lesion, but because of the distinct hemorrhagic infarction could not determine whether it was benign or malignant. As shown in this case, when the radiological result is ambiguous, renal exposure is indicated from both a diagnostic and therapeutic standpoint.

Purpose: The biological behavior and clinical outcome of renal cell carcinoma are difficult to predict. We investigated the prognostic impact of clinicopathological variables to establish a risk stratification model to predict recurrence and survival rates., Materials and Methods: We studied 230 patients with renal cell carcinoma (stages T(1-4) N(x) M(0)) who underwent radical nephrectomy and/or nephron sparing surgery, and were followed for a median of 48 months (range 3 to 140). Univariate and multivariate analyses were performed, and the influence of clinical presentation, histological tumor size, tumor grade, lymph node involvement and microvascular tumor invasion on disease-free and cancer specific survival curves was determined. A composition model based on independent prognostic variables was then created to stratify tumors into low, intermediate and high risk of progression., Results: The tumor recurrence rate was 17% (39 of 230) and the cancer specific mortality rate was 13% (31 of 230). Multivariate analyses determined that microvascular tumor invasion, tumor grade and tumor size were the only independent prognostic factors. Disease-free survival rates for low, intermediate and high risk tumors were 94.7%, 56.8% and 13.1%, respectively. Cancer specific survival rates were 94.7%, 61.7% and 32.0%, respectively., Conclusions: Tumor size, Fuhrman grade and microvascular tumor invasion are strong and independent predictors of survival of patients with renal cell carcinoma. Risk assessment and stratification based on this triad of pathological features may allow better individualization of followup schedules and trials of adjuvant treatment for patients with renal cell carcinoma.

Purpose: To prospectively determine whether modulation of renal cell carcinoma (RCC) tumor microvasculature by using the antiangiogenic drug sorafenib could increase the extent of radiofrequency (RF)-induced coagulation in an RCC animal tumor model., Materials and Methods: All investigations received animal care and utilization committee approval. RCC (human 786-0) was implanted subcutaneously into 27 nude mice. Sixteen mice were randomly assigned into one of three groups when tumors reached 12 mm in diameter: Six mice received 80 mg of sorafenib, a Raf kinase and vascular endothelial growth factor receptor inhibitor, per kilogram of body weight; five mice received 20 mg/kg sorafenib; and five mice received a control carrier vehicle alone. Antiangiogenic therapy was administered until a mean 1-mm reduction in tumor diameter was noted in one group. These 16 mice received a standard dose of RF ablation. Ablation size was visualized by using 2% triphenyltetrazolium chloride. An additional 11 tumors in mice treated with sorafenib alone were stained with CD31 to determine microvascular density (MVD). Resultant size of ablation was compared among groups; statistical significance was determined with analysis of variance. Differences in MVD were assessed with the Kruskal-Wallis test., Results: Over the 9-day administration of sorafenib, mean tumor size in the control group reached 15.2 mm +/- 0.8 (standard deviation). Tumors in mice receiving 20 mg/kg and 80 mg/kg sorafenib measured 12.2 mm +/- 0.6 and 11.1 mm +/- 0.5, respectively (P < .05). RF-induced coagulation diameter was 8.5 mm +/- 0.4 and 11.1 mm +/- 0.3 in the 20 mg/kg and 80 mg/kg sorafenib groups, respectively, but was only 6.7 mm +/- 0.7 for animals that underwent RF ablation alone (P < .01). Likewise, significant decreases in MVD were noted in the sorafenib-treated animals (P < .01)., Conclusion: Treatment of RCC in nude mice with the antiangiogenic agent sorafenib resulted in markedly decreased MVD and significantly larger zones of RF-induced coagulation necrosis.

Purpose: To analyze local recurrence-free rates and risk factors for recurrence following percutaneous radiofrequency ablation (RFA) or transcatheter arterial chemoembolization (TACE) for hypervascular hepatocellular carcinoma (HCC)., Methods: One hundred and nine nodules treated by RFA and 173 nodules treated by TACE were included. Hypovascular nodules were excluded from this study. Overall local recurrence-free rates of each treatment group were calculated using the Kaplan-Meier method. The independent risk factors of local recurrence and the hazard ratios were analyzed using Cox's proportional-hazards regression model. Based on the results of multivariate analyses, we classified HCC nodules into four subgroups: central nodules < or =2 cm or >2 cm and peripheral nodules < or =2 cm or >2 cm. The local recurrence-free rates of these subgroups for each treatment were also calculated., Results: The overall local recurrence-free rate was significantly higher in the RFA group than in the TACE group (p = 0.013). The 24-month local recurrence-free rates in the RFA and TACE groups were 60.0% and 48.9%, respectively. In the RFA group, the only significant risk factor for recurrence was tumor size >2 cm in greatest dimension. In the TACE group, a central location was the only significant risk factor for recurrence. In central nodules that were < or =2 cm, the local recurrence-free rate was significantly higher in the RFA group than in the TACE group (p < 0.001). In the remaining three groups, there was no significant difference in local recurrence-free rate between the two treatment methods., Conclusion: A tumor diameter of >2 cm was the only independent risk factor for local recurrence in RFA treatment, and a central location was the only independent risk factor in TACE treatment. Central lesions measuring < or =2 cm should be treated by RFA.

Recent studies indicate that portions of ischemic and tumor neovasculature are derived by neovasculogenesis, whereby bone marrow (BM)-derived circulating endothelial progenitor cells (EPCs) home to sites of regenerative or malignant growth and contribute to blood vessel formation. Recent data from animal models suggest that a variety of cell types, including unfractionated BM mononuclear cells and those obtained by ex vivo expansion of human peripheral blood or enriched progenitors, can function as EPCs to promote tissue vasculogenesis, regeneration, and repair when introduced in vivo. The promising preclinical results have led to several human clinical trials using BM as a potential source of EPCs in cardiac repair as well as ongoing basic research on using EPCs in tissue engineering or as cell therapy to target tumor growth.

This observational case report is designed to report the first known occurrence of Familial Exudative Vitreoretinopathy (FEVR) and macular hole in the same individual. Clinical exams and fluorescein angiography were used to evaluate patient. Indirect laser panretinal photocoagulation was used to treat the right eye. A nine-year old male was diagnosed with familial exudative vitreoretinopathy in both eyes, as well as a full-thickness macular hole in his right eye. Medical histories indicated that the macular hole was not caused by trauma. Indirect laser panretinal photocoagulation was performed to treat an exudative process caused by FEVR in the right eye, and the exudative retinal detachment regressed. A vitrectomy was later also performed to treat traction retinal detachment as well as macular hole in the right eye. Our conclusion is that macular hole can be associated with familial exudative vitreoretinopathy.

Background and Objective: To compare the effects of panretinal photocoagulation (PRP) and photodynamic therapy (PDT) for anterior segment neovascularization secondary to ischemic central retinal vein occlusion (CRVO)., Patients and Methods: Fifty-seven eyes were randomized to receive standard PRP (19 eyes), selective PRP (20 eyes), or PDT (17 eyes). Selective PRP was performed only when iris neovascularization and/or angle neovascularization showed progression on weekly follow-up. Primary outcome measures were the extension of anterior segment neovascularization and the rate of neovascular glaucoma development. Secondary outcome measures included visual acuity results., Results: After 12 months of follow-up, iris neovascularization extension was 0.52, 2.55, and 2.27 in the PRP, selective PRP, and PDT groups, respectively. Anterior segment neovascularization extension was 0.57, 1.50, and 1.27 in the PRP, selective PRP, and PDT groups, respectively. Both showed a statistically significant difference in the PRP group. The rate of neovascular glaucoma development was similar in the three groups., Conclusions: Although PRP was better at determining iris neovascularization and anterior segment neovascularization regression, the similar rate of neovascular glaucoma development found in the three groups indicates that anterior segment neovascularization secondary to ischemic CRVO can also be safely managed using selective PRP or PDT.

Aim: To compare the angiogenesis in anal canal carcinomas (ACC) with that in colorectal carcinomas (CRC)., Methods: A number of 507 CRC, surgical specimens, were analyzed, 12 cases (1.97%) being ACC. In 20 cases from left and right colon (CRC) and in the 12 ACC we analyzed the immunohistochemical parameters related to angiogenesis, utilizing the following LabVision antibodies: CD31, CD105 (endoglin) and VEGF1. Morphometrical analysis and positive cell counting were performed in the tumoral and peritumoral tissue. Immunoperoxidase method was used., Results: The average age was 63.17 +/- 10.87 years in CRC, respectively 57.9 +/- 10.05 years in the ACC (p<0.0001). Compared with CRC the ACC occur more frequently at the females (58%). Angiogenesis was expressed in the majority of cases. In CRC, the microvascular density (MVD) was higher than that from ACC. The ratio CD31/CD105 was 1 in ACC and 3 in CRC. VEGF was positive in 25% of ACC and 80% of CRC. In CRC were more mature vessels, marked only with CD31 than immature vessels or endothelial isolated cells marked with both CD31 and CD105. In ACC prevailed the neoformed vessels marked with both CD31 and CD105., Conclusions: The performed assessments have showed a higher incidence of ACC at females and at younger ages. The angiogenesis in ACC was not so high like in CRC and the immature neoformed vessels was more frequently. In ACC, the antiangiogenic treatment that regards the VEGF inhibition seems to be not as efficient as in CRC. The radiotherapy could stop the angiogenesis and could inhibit the vessels' maturation.

Survival rates were studied in 57 patients with primary liver carcinoma (including 32 with hepatocellular carcinoma [HCC] and 25 with cholangiocellular carcinoma [CCC] in relation to the histological type of a tumor and its microcirculatory bed. In all the patients, tumor resection was performed, followed by chemoemlolization of the liver. The development of tumor microvessels was assessed by the sum of their perimeters. If the size of a vessel was higher than its median, overall survival was 19.3 months, if the size was lower, it was increased by an average of 86.7 months. In patients with CCC, survival did not depend on tumor angiogenesis and it averaged 19.7 months.

We report the feasibility and efficacy of percutaneous injection of Onyx (Micro Therapeutics, Irvine, Calif.), a nonadhesive liquid embolic agent, into an unusually located paraganglioma, followed by endovascular embolization with particles before surgery.

Object: Cystic vestibular schwannoma (VS) is a unique subgroup of VSs characterized by unpredictable expansion of the cyst component. Little is known, however, about the mechanism of cyst formation. In this study the authors compared neuroimaging and histological characteristics of cystic with solid VS to determine the pathogenesis of the cystic subgroup., Methods: Two cohorts, one comprising 10 patients with cystic VS and the other comprising 10 patients with solid VS, were studied. Surgery was chosen as the primary treatment in all patients, with no other modality applied. Preoperative magnetic resonance images and histological characteristics of the tumor in patients with cystic VSs were evaluated and compared with those in the group with solid VSs. Differences between the two groups were assessed using the chi-square test. Neuroimaging findings revealed that either fluid-fluid level or hemosiderin deposit was present in all cystic VSs. Histological evidence of microhemorrhage, such as hemosiderin-laden macrophages (p = 0.069), hemosiderin deposits (p = 0.019), thrombotic vessels (p = 0.008), and abnormal vessel proliferation (p = 0.006) were more prominent in cystic VSs compared with solid ones. There was no difference in Antoni type dominance and Ki-67 proliferative index between the two groups., Conclusions: Intratumoral microhemorrhage is a possible mechanism of pathogenesis in cystic VS.

Background: High resolution colour Doppler ultrasound shows intratendinous Doppler activity in patients with chronic Achilles tendinopathy. Treatment of this neovascularisation with sclerosing therapy seems to relieve the pain. However, the procedure often has to be repeated., Objective: To investigate the effect of electrocoagulation of the neovessels on tendon pain and tendon vascularity in patients with chronic Achilles tendinopathy., Methods: Colour Doppler ultrasound guided electrocoagulation was used on vessels in the ventral portion of the Achilles tendon in 11 patients (seven men, four women, mean age 41 years) with painful chronic mid-portion Achilles tendinosis. A unipolar coagulation device was used., Results: One patient dropped out after two months (dissatisfied with the results). The remaining 10 patients (91%) were satisfied. These 10 patients were still satisfied at six months of follow up and had returned to their previous level of activity. All 10 patients were "cured" after one treatment. The patient who dropped out received two treatments because of lack of progress. There was significantly reduced pain (Likert pain scale, 0-10) during activity, from a median of 7 (range 4 to 10) at baseline to 0 (0 to 8) at six months' follow up (p<0.005); and at rest, from 1.5 (1 to 5) to 0 (0 to 8) (p = 0.005). In all patients, vascularisation was unchanged at the six months follow up, with no significant change in semiquantitative or quantitative colour scoring., Conclusions: Coagulation in the area with vessels entering the tendon appears to be effective treatment for painful chronic mid-tendinous Achilles tendinopathy. No effect on the intratendinous Doppler activity could be detected, suggesting that the effect is independent of changes in blood flow. Localisation of hyperaemia appears to be the key to the pathology and for targeting the treatment. One explanation could be that the effect is obtained by destruction of nerves accompanying the vessels.

A case of hepatobiliary cystadenoma with mesenchymal stroma and a case of biliary cystadenocarcinoma are presented. Hepatobiliary cystadenoma and cystadenocarcinoma are rare liver lesions that are difficult to diagnose preoperatively. Regardless of the diagnostic modalities used these two pathologies cannot be differentiated with accuracy. The preoperative diagnosis of biliary cystadenoma and cystadenocarcinoma was suggested due to the radiological detection of vascularity in the septa and the invasion of the thoracoabdominal wall. The surgeon was informed in both of the cases. Pathologic examination confirmed the diagnosis in both of our patients. The radiological features of these pathologies are discussed in detail together with a brief review of the literature.

We report a case of a primary lymphoepithelioma-like carcinoma (LELC) of the skin. The patient was a 73-year-old man with a lump on his back for 18 months. A biopsy and subsequent excision was performed. He also had axillary node clearance for metastatic disease. The tumor was composed of islands of pleomorphic cells with a lymphocytic infiltrate. Differential diagnoses included squamous cell carcinoma, adnexal carcinoma, Merkel cell tumors, lymphoepithelial lesions, lymphomas, and skin metastases. The histopathologic and immunohistochemical features were those of a LELC of the skin. It was negative for Epstein-Barr virus. Just over 30 cases of primary LELCs arising in the skin have been reported with only 1 documented fatality. We report a case with extensive vascular involvement and bilateral lymph node metastases.

Object: The authors' aim in conducting this study was to investigate retrospectively the prognostic significance of angiogenic features in optic pathway/hypothalamic gliomas (OPHGs) in children., Methods: Patients were identified in whom a diagnosis of OPHG was made using pathological analysis at the Toronto Hospital for Sick Children between 1985 and 2002. Tumor specimens were reviewed for diagnostic accuracy and adequacy of the specimen. Sections were immunostained with factor VIII to assess microvessel density (MVD). A ratio of alpha-smooth muscle actin to factor VIII immunostaining was calculated to arrive at a vascular maturity index (VMI). Vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) immunostaining were performed to evaluate angiogenic factors. In addition, the MIB-1 labeling index (LI) was used to assess proliferation. These factors were evaluated with respect to progression-free survival (PFS). Forty-one of 60 patients originally identified had adequate samples and follow up for inclusion in the study. Of these, eight patients had coexisting neurofibromatosis Type 1. Twenty-eight patients experienced tumor progression after the initial treatment (surgery with or without adjuvant treatment). Thirty-eight patients are still alive. A high MVD (> 21 vessels/1.2 mm2) was associated with a significantly higher rate of progression compared with a low MVD (< 21 vessels/1.2 mm2; p = 0.017). Microvessel density was also predictive of reduced PFS on multivariate analysis stratified for extent of resection (p = 0.04), and VMI as well as intensity and distribution of VEGF and VEGFR staining and the MIB-1 LI were not significantly associated with PFS., Conclusions: These findings suggest that MVD is the best current predictor of PFS in incompletely resected OPHGs. This information highlights the importance of angiogenesis in regard to low-grade gliomas.

Using monochromatic synchrotron radiation, we performed microangiography in C57BL/6J mice and investigated their vasculature after unilateral and bilateral carotid artery occlusion. Bilateral occlusion of the carotid artery was made by a ligation of the left common carotid artery followed by a ligation of the right internal carotid artery (ICA) two days later (n=12). Five days after the second surgery, angiography was performed. Unilateral occlusion was made by clipping the right ICA and then angiography was performed immediately (n=5). The control mice did not undergo any occlusion (n=5). We removed the brain of the bilateral occlusion mice after angiography and examined the infarction area. The cerebral microvessels in all animals were clearly visualized. In the control mice, the posterior communicating artery (Pcom) was not visualized. In the unilateral occlusion mice, the anastomosis of the pterygopalatine artery (PPA) and the external carotid artery (ECA) were recognized. The PPA is thus considered to play a role in the collateral vessel between the ICA and the ECA. The Pcom was not visualized. In the bilateral occlusion mice, the Pcom was observed either unilaterally (n=5) or bilaterally (n=5). The Pcom supplied blood flow to the anterior circulation from the vertebrobasilar arteries. The bilateral occlusion mice that had at least one visualized Pcom did not have any infarction. We could successfully visualize the cerebral vasculature of normal mice and carotid artery occluded mice in an in vivo study. Microangiography can demonstrate the development of vasculature and the blood flow dynamics in mice.

Objectives: We sought to evaluate the contribution of unifocalization procedures in the management of patients with pulmonary atresia, ventricular septal defect, and major aortopulmonary collateral arteries., Methods: From 1975 through 1995, 82 consecutive patients were entered in a multistage approach and had 189 sternotomies and thoracotomies to perform 119 shunts, 130 major aortopulmonary collateral artery transplantations, and 76 major aortopulmonary collateral artery ligations. The serial angiographies and the follow-up of these patients were reviewed., Results: The concurrent follow-up rate was 80%. The hospital mortality of the preliminary procedures was 4% (7/189). Fifty-three (65%) patients had a complete repair. The hospital mortality of the repair was 8% (4/53), and 9 late deaths occurred after repair, all of which were cardiac related. The overall survival of all patients to the age of 30 years was 58% +/- 7%. Survival 12 years after complete repair was 51% +/- 14%. On angiography, central shunts promoted growth of central pulmonary arteries in all cases (29 patients). Sixty unifocalized major aortopulmonary collateral arteries were identified in 31 patients. After a mean of 3.2 +/- 4 years, 26 thrombosed, and 12 presented with a stenosis of greater than 50%. Serial measurements of 29 major aortopulmonary collateral arteries showed no signs of growth (P = .25)., Conclusion: Long-term survival into adulthood of patients with pulmonary atresia, ventricular septal defect, and major aortopulmonary collateral arteries has been achieved with a multistage approach. However, late survival depends exclusively on the growth of the native pulmonary circulation. The few unifocalized major aortopulmonary collateral arteries that did not thrombose failed to grow.

Lower-limb ischemia is a major health problem. Because of the absence of effective treatment in the advanced stages of the disease, amputation is undertaken to alleviate unbearable symptoms. Novel therapeutic approaches include the intramuscular use of autologous bone marrow cells (BMCs). Because tissue ischemia is associated with an overwhelming generation of oxygen radicals and negative effects due to perturbed shear-stress, metabolic intervention with antioxidants and l-arginine could potentially induce beneficial effects beyond those achieved by BMCs. The protective effect of autologous BMCs and vascular protection by metabolic cotreatment (1.0% vitamin E added to the chow and 0.05% vitamin C and 6% l-arginine added to the drinking water) were examined in ischemia-induced angiogenesis in the mouse hindlimb, a model of extensive acute peripheral arterial occlusion. i.v. BMC therapy improved blood flow and increased capillary densities and expression of Ki-67, a proliferation-associated protein. This beneficial effect was amplified by metabolic cotreatment, an intervention inducing vascular protection, at least in part, through the nitric oxide pathway, reduction of systemic oxidative stress, and macrophage activation. Therefore, although a cautious approach is mandatory when experimental findings are extended to human diseases, autologous BMCs together with metabolic intervention could be an effective clinical treatment for peripheral arterial disease.

Objectives: To investigate the prognostic value of potential markers in localized, Gleason score 6 and 7 prostate cancer (PC)., Methods: From a consecutive series of men with PC diagnosed at transurethral resection (1975-1990), specimens from 132 patients without metastases, with Gleason score (GS) 6 (n=80) or 7 (n=52) tumors followed with watchful waiting were examined. The fraction of resected prostate tissue containing cancer, the micro-vessel density (v.d.) when stained for endoglin or von Willebrand factor (vWf), and the percentage of Ki-67 labeled tumor cells were measured using immunohistochemistry., Results: High levels of vWf v.d., endoglin v.d., and percent cancer of the TURP specimen were significantly associated with short cancer-specific survival in Kaplan-Meier analysis of all patients with GS 6 and 7 tumors. Interestingly, a combined estimate of percent cancer and vWF v.d. could be used to identify a large subset (50%) of GS 6 tumors with only a 2.5% risk of PC death within 15 years. None of the tested markers gave independent prognostic information for the GS 7 tumors., Conclusions: Estimates of tumor size and vascular density may identify a large proportion of non-aggressive GS 6, but not GS 7, tumors.

A unique case of repeatedly intussuscepted colonic lipoma mimicking an epithelial tumor in a 50-year-old man is reported. The tumor was located in the ascending colon and was approximately 5 cm in diameter. Colonoscopic and barium-enema examinations suggested a huge epithelial tumor because of its nodule-aggregating appearance. In contrast, computed tomography examination showed a fatty element in the core of the lesion. The biopsy specimens suggested a primary angiomatous lesion because of its pronounced vascular proliferation. Because the presumed diagnoses based on the examinations were different, the preoperative diagnosis was not confirmed. The tumor was composed of intramural lipoma with a multiple polypoid mucosa overlay. This lesion was unique in that the lipoma appeared to be within the muscularis propria and the multiple polypoid appearance of its covering mucosa. The mucosal changes including florid vascular proliferation, fibromuscular obliteration and epithelial regeneration suggested a reparative process, with ischemic damage due to the effects of intussusception being the most likely event. It should be kept in mind that even a simple lipoma can have a unique appearance reminiscent of epithelial tumor when it repeatedly experiences intussusception.

Object: The goal of this study was to evaluate intraoperative power Doppler ultrasonography when used with a contrast-enhancing agent for operations on intracranial tumors., Methods: Forty intracranial tumors were examined using power Doppler ultrasonography with a galactose microparticle-based ultrasonographic contrast-enhancing agent during operations on the brain. The tumors included 37 intracranial neoplasms (14 gliomas, six meningiomas, three hemangioblastomas, two malignant lymphomas, three other primary neoplasms, nine metastatic tumors, and three nonneoplastic lesions). All patients also underwent computerized tomography and magnetic resonance imaging, and all but three of the patients underwent digital subtraction (DS) angiography. Before injection of the ultrasonographic contrast agent, intra- and peritumoral power Doppler flow signals were detected in 32 of the intracranial tumors. After the injection, the signals were enhanced in blood vessels around the tumors and in the tumor parenchyma in 36 tumors. The duration of contrast enhancement continued for 70 to 365 seconds (mean 251.8 +/- 69 seconds) after the injection. Among the tumors, hemangioblastomas displayed particularly strong contrast enhancement. In these intracranial tumors, the echo signals obtained using contrast-enhanced power Doppler ultrasonography correlated with DS angiographic staining. Power Doppler ultrasonograms with the appropriate contrast agent provided better data on the precise real-time position of the tumors and their relationship to adjacent vessels than ultrasonograms obtained before the injection of the contrast agent., Conclusions: Intraoperative power Doppler ultrasonography performed using a contrast-enhancing agent can facilitate intraoperative real-time navigation and assessment of the intratumoral vasculature and peritumoral vessels, particularly for tumors having abundant vessels such as hemangioblastomas.

Object: Cerebral cavernous malformations (CCMs) have previously been considered as congenital and biologically static malformations. On the other hand, the potential for growth and de novo generation of CCMs have also been reported. It is therefore important to study the proliferative and neoangiogenetic capacity of these lesions., Methods: The authors studied the surgical specimens of 56 CCMs (23 deep and 33 superficial) obtained from adult patients. The proliferative activity of the endothelium and the neoangiogenetic capacity of these lesions were considered through immunohistochemical anaylsis of proliferating cell nuclear antigen (PCNA), MIB-1, Flk-1, vascular endothelial growth factor (VEGF), hypoxia-inducible factor (HIF)-1alpha, and endoglin antibodies. Positive immunostaining of endothelial cells occurred in 86% of patients for PCNA and in 38% of the cases for MIB 1. The expression of Flk-1 was observed in the endothelium of 71% of the cases, for VEGF in 41%, for HIF-1 alpha in 48.1%, and for endoglin in 63.6% of the cases. The correlation of immunohistochemical and clinical data indicated that VEGF was expressed in significantly less deep-seated lesions when compared with superficial CCMs. Neither the expression of the proliferative markers nor the expression of the angiogenetic antibodies correlated with patient age at surgery, sex, or the number of recent prior hemorrhagic episodes in the patients., Conclusions: The CCMs from adult patients are active lesions exhibiting endothelial proliferation and neoangiogenesis. According to the data in this study, neoangiogenesis is more prominent in superficial CCMs than in deep-seated CCMs and is not associated with recent prior hemorrhages.

Objective/hypothesis: Paragangliomas are heavily vascularized tumors, and the expression of VEGF (vascular endothelial growth factor) has been reported. The aim of our study was to extend the available database of VEGF expression in paraganglioma, to add correlated data concerning vessel density and proliferative activity, and to draw conclusions concerning the mechanisms resulting in tumor vascularization and growth., Study Design: Semiquantitative histopathologic examination of paraganglioma specimens obtained from surgical cases., Methods: Paraffin-embedded paragangliomas were analyzed by immunohistochemistry. Fourteen consecutive samples were hybridized with VEGF-, CD31- and Ki67-specific antibodies, and visualized by diaminobenzidine staining. Vessel density was determined by counting CD31-positive vessels and proliferation by quantification of Ki67-positive cells., Results: Ten out of 14 samples were positive for VEGF. In this group, vessel density was up to 5 times as high and proliferative activity was about twice as high as in the VEGF-negative group., Conclusions: We observed higher CD31 and Ki67 counts in VEGF-positive tumors, but statistical significance could not be assessed due to low sample numbers. These data might suggest a contribution of VEGF secreted by paragangliomas to tumor vascularization and possibly proliferation. The clinical impact of VEGF expression analysis has to be proven in future studies., (Copyright 2005 S. Karger AG, Basel.)

Vascular abnormalities of the intestines are unusual. We present a florid benign vascular proliferation of the jejunum in one adult patient, presented with intussusception. In this cases, the proliferation was sufficiently exuberant to raise the possibility of angiosarcoma as a diagnostic consideration. The patient was 81-years old female. The main clinical symptoms at presentation included abdominal pain and bowel obstruction. On exlorative laparotomy two jejunal masses were found. Histologically in these lesions a florid lobular proliferation of small vascular channels lined by plump endothelial cells extended from the submucosa through the entire thickness of the bowel wall. The endothelial cells showed minimal nuclear atypia, and mitotic figures were infrequent. The overlying mucosa showed ulceration with ischemic-type changes, and had features of mucosal prolapse. The presence of intussusception or mucosal prolapse in the case suggests repeated mechanical forces applied to the bowel wall as a possible etiologic factor.

Hemangiopericytomas are rare perivascular tumors. The nasal cavity and paranasal sinuses are most often involved in the head and neck region. A case of hemangiopericytoma in a 63 year old patient is presented. The initial symptom was recurrent bleeding from the nose. The patient had a history of radiotherapy for a pituitary adenoma 30 years previously. Computed tomography and magnetic resonance imaging showed a polypoid opacification of the ethmoid, sphenoid and basal aspects of the frontal sinus on the right side. Histological diagnosis was obtained from nasal biopsy. Preoperatively, arteriography and tumor embolisation were performed. The tumor was completely excised using a combined endonasal and external approach as an osteoplastic revision of the frontal sinus via bicoronal incision. There was no recurrence at follow-up 1 year later.

Purpose: Neovascular glaucoma is a frequent complication of vitrectomy performed to treat proliferative diabetic retinopathy (PDR). We assessed the level of vascular endothelial growth factor (VEGF) in the vitreous fluid obtained during vitrectomy and at postoperative fluid-air exchange., Methods: We measured VEGF levels in vitreous samples from 17 eyes of 15 patients with PDR during vitrectomy and fluid samples obtained during fluid-air exchange 5 to 36 days postoperatively. Six of the 17 eyes had iris neovascularization after vitrectomy. Vascular endothelial growth factor levels also were measured in the vitreous fluid obtained from 8 eyes with a macular hole during vitrectomy and postoperative fluid-air exchange. We measured the plasma VEGF levels in all patients., Results: The mean VEGF levels in 17 eyes with PDR were 1162.3+/-173.2 pg/ml in the vitreous samples and 1180.4+/-182.8 pg/ml in the postoperative fluid samples. The mean plasma VEGF level was 116.1+/-10.2 pg/ml in eyes with PDR, and the mean plasma VEGF level was 118.5+/-15.2 pg/ml in patients with a macular hole. The mean VEGF levels were 96.9+/-11.5 pg/ml in the vitreous samples and 73.9+/-12.3 pg/ml in the fluid samples in eyes with a macular hole., Conclusions: A high VEGF level was maintained in the vitreous cavity after vitrectomy for PDR. The VEGF level in eyes with PDR was 10 times higher than that in the plasma. The results suggest that there is persistent secretion of VEGF into the vitreous cavity even after vitrectomy for PDR.

Objective: In previous studies, we documented a marked neoangiogenesis and endothelial proliferation in cerebral arteriovenous malformations (AVMs) that were embolized before surgery compared with those that were not embolized. We hypothesized that embolization caused a local hypoxia that promotes neoangiogenesis as a possible pathomechanism. To support this hypothesis, we now examined the angiogenesis-related proteins in a larger cohort of patients. In addition, we investigated hypoxia-inducible factor-1 alpha as a possible protein operative during neoangiogenesis of cerebral AVMs., Methods: Paraffin-embedded specimens of 56 AVMs obtained from surgical resection and 14 brain tissue controls were immunohistochemically stained with antibodies to proliferating cell nuclear antigen, MIB-1, vascular endothelial growth factor, Flk1, and hypoxia-inducible factor-1 alpha by standard protocols., Results: In AVMs treated with embolization before surgery (n = 35, 63%), the expression of hypoxia-inducible factor-1 alpha (P = 0.0101) and vascular endothelial growth factor (P = 0.0007) was significantly higher (Fisher's exact test) than in patients who did not have previous endovascular treatment. Differences in the expression of Flk-1 (P = 0.0798) and proliferating cell nuclear antigen (P = 0.0423) were in the same direction but were not significant when corrected for multiple testing., Conclusion: Our results provide circumstantial evidence that a partial occlusion of cerebral AVMs might induce local hypoxia-related neoangiogenesis. To support these data, future animal studies should be performed.

Background: The surgical removal of solid, large, and deep-seated hemangioblastomas remains challenging because it is difficult to control bleeding during the procedure. We used preoperative radiosurgery in a solid, highly vascular hemangioblastoma at the left cerebello-pontine angle and present our angiographic, operative, and histologic findings., Case Description: A 37-year-old paraplegic woman with multiple hemangioblastomas was re-admitted to our clinic with cerebellar ataxia 6 years after resection of a tumor at the fourth ventricle. A vertebral artery angiogram revealed that the 3.5 cm diameter hemangioblastoma at the left cerebello-pontine angle was highly vascular and fed by the left anterior inferior cerebellar artery and posterior inferior cerebellar artery. Nine months before surgical removal it was treated with stereotactic radiosurgery (gamma knife, margin dose 28 Gy) to inhibit tumor progression and to reduce its vascularity. The tumor was totally removed via the left lateral suboccipital approach; bleeding was well controlled and there were no complications. Pathologic examination of the content of the excised tumor revealed coagulation necrosis with hyaline degeneration of the tumor vessels, resulting in a marked decrease in its vascularity., Conclusion: Preoperative radiosurgery led to a marked reduction in the vascularity of this hypervascular hemangioblastoma and was useful for controlling bleeding from the tumor during resection. We succeeded to remove the vascular-rich hemangioblastma after the intentional preoperative radiosurgery. The pathologic changes induced by radiotherapy were confirmed by operative finding.

Recent evidence suggests that androgens stimulate growth of human prostate cancer partly by regulating expression of growth factors such as vascular endothelial growth factor (VEGF) in vitro and in vivo. In this study, we used CWR22Rv1, a novel androgen-responsive but androgen-independent human prostate cancer model, to evaluate the effect of androgen withdrawal on tumor growth, expression of VEGF and the cell proliferation marker Ki-67, and angiogenesis. A time-release testosterone pellet was implanted three days before inoculation of CWR22Rv1 cells in the mice. The tumor volumes were measured every three days. Serum PSA was measured on days 1, 12, 20, 27 and 34 post inoculation. Castration was performed on the 20th day post inoculation. Immunohistochemical assays were used to evaluate cell proliferation and microvessel density. Enzyme-linked immunosorbent assay (ELISA) was used to quantify VEGF expression. The average tumor volumes in the castration group on the 27th and 34th days were 122 and 168 mm3, respectively, compared to 156 and 210 mm3 in the non-castration group (p<0.01). Serum PSA level in the castration group decreased to about 41% of the level of the non-castration group (p<0.01). The VEGF protein levels in the tumors of castrated and non-castrated mice on day 34 were 0.62 pg and 1.36 pg/100 microg total protein, respectively (p<0.001). The mean percentage of Ki-67-positive tumor cells in the castrated and non-castrated groups were 1.8% and 2.8%, respectively (p=0.015). The mean microvessel densities in the castrated and non-castrated groups were 15 and 22 vessels/field, respectively (p<0.01) We conclude androgen withdrawal reduced both VEGF and microvessel density, and this was associated with decreased cellular proliferation in androgen-independent CWR22Rv1 human prostate cancer tumor in vivo.

A case of asynchronous bilateral breast necrosis in a 40-year-old woman with untreated chronic hypercholesteraemia is described. Mastectomies were performed, and histological examination revealed bilateral breast calciphylaxis characterized by extensive vascular calcification with coagulative necrosis. Breast calciphylaxis is a rare disease clinically characterized by progressive tissular necrosis with secondary cutaneous ulceration and by vascular calcification and thrombosis. However, the nature of the vascular calcification has remained poorly understood up to now, owing to the absence of any precise mineralogical examination. In this case the mineral deposits were analysed for the first time: only hydroxyapatite was found. The etiology is discussed, and the high cholesterol rate of the patient is implicated., (Copyright 2004 Elsevier Ltd.)

Myxoma is the most common benign tumor of the heart. Tumor neovascularization at the angiographically detectable level is thought to be rare. We report on a 78-year-old female patient with a left atrial myxoma showing marked tumor vascularity. This observation had consequences to the therapeutic management: during tumor excision, the large supplying artery had to be ligated.