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Objective: To evaluate whether suppression of tumor microvasculature by double anti-angiogenic protein (DAAP) treatment could increase the extent of radiofrequency ablation (RFA)-induced coagulation in a murine renal cell carcinoma model., Materials and Methods: Renal cell carcinoma cell lines were implanted subcutaneously into 10 nude mice. Four mice received adenoviral DAAP treatment and 6 mice received sterile 0.9% saline solution as DAAP-untreated group. The effect of DAAP was evaluated according to the vascularity by contrast-enhanced ultrasound (CEUS) using microbubbles. Four DAAP-treated mice and 4 DAAP-untreated mice were then treated with RFA, resulting in 3 groups: no-therapy (n = 2), RFA only (n = 4), and RFA combined with DAAP treatment (n = 4). Immediately after RFA, the size of coagulation necrosis and mitochondrial enzyme activity were compared between the groups using analysis of variance (ANOVA) and post hoc test., Results: The contrast enhancement ratio for tumor vascularization on CEUS was significantly lower in the DAAP treated group than in DAAP-untreated group (30.2 ± 9.9% vs. 77.4 ± 17.3%; p = 0.021). After RFA, the mean coagulation diameter was 0 mm for no-therapy group, 6.7 ± 0.7 mm for the RFA only group and 8.5 ± 0.4 mm for the RFA with DAAP group (ANOVA, p < 0.001). The area of viable mitochondria within the tumor was 27.9 ± 3.9% in no-therapy group, 10.3 ± 4.5% in the RFA only group, and 2.1 ± 0.7% in the RFA with DAAP group (ANOVA, p < 0.001)., Conclusion: Our results suggest the potential value of combining RFA with anti-angiogenic therapy.

Background: Vascular invasion (VI) is an important predictor of distant metastasis and possible radioactive iodine (RAI) benefit in follicular, Hürthle cell, and poorly differentiated thyroid carcinomas, but its role in well-differentiated papillary thyroid cancer (WDTC) remains unclear., Methods: Archived pathological material of all differentiated thyroid carcinoma patients undergoing primary surgical treatment at Memorial Sloan-Kettering Cancer Center between 1986 and 2003 was reviewed by two dedicated thyroid pathologists. Only WDTCs were included in the present study. Standard statistical methods were used to assess the relationship between VI and outcomes of interest, including 10-year disease-specific survival (DSS), regional recurrence-free survival (RRFS), and distant recurrence-free survival (DRFS)., Results: VI was present in 47 of 698 WDTC (6.7%). VI was significantly associated with tumor size >4.0 cm, extrathyroidal extension, distant metastasis, and RAI treatment. On univariate analysis, VI was predictive of decreased 10-year DRFS, but not DSS or RRFS. On multivariate analysis, VI was not an independent predictor of DRFS. Univariate survival analysis of 422 RAI-naïve WDTC showed that both size >4 cm and VI were predictors of outcome, but only size remained independently predictive on multivariate analysis., Conclusion: The presence of VI is not an independent predictor of outcome in WDTC.

Background and Purpose: To more safely resect pathological lesions during spinal vascular lesion surgery, it is most important to understand local abnormal hemodynamics in detail. New devices or techniques that make out intraoperative local hemodynamics have been awaited. To introduce a resourceful method, we present a case of spinal hemangioblastoma for which temporary arterial occlusion during near-infrared intraoperative indocyanine green (ICG) videoangiography gives useful assessment of the main and minor feeders easily., Methods: A 36-year-old female suffered progressive paresthesia of both lower extremities for 12 months and gait disturbance for 2 weeks. A neurological examination revealed T10 myelopathy. Magnetic resonance imaging (MRI) of the thoracic spine showed an intramedullary tumor at the T8 level and severe spinal cord edema with a flow void in the extended dorsal spinal veins. Spinal angiography showed a hemangioblastoma at the T8 level, with two main feeders and minor feeders., Results: She underwent total resection of the tumor by a posterior approach. During the intraoperative ICG videoangiography, temporary arterial occlusion of the two main feeders and FLOW(®)800 analysis enabled clear understanding of the vasculature, especially of the two minor feeders. At the 9-month follow-up, her neurological manifestation was partially resolved, and post-operative MRI showed total removal of the tumor and disappearance of the spinal cord edema., Conclusions: Temporary clipping of the main feeders during intraoperative ICG videoangiography is very useful for easily determining the minor feeding arteries, and helpful for maintaining normal perfusion of the spinal cord in spinal hemangioblastoma surgery. Furthermore, the FLOW 800 analysis, especially the false color-coded variation, increased our understanding of the hemodynamics.

The prognostic significance of vascular invasion (VI) in nonmetastatic gastric cancer (GC) remains a matter of controversy. The purpose of this study was to assess the impact of VI on survival in this group of GC patients. We enrolled 361 GC patients without metastasis who underwent curative gastrectomy between 1996 and 2009 in Sun Yat-sen University Cancer Center. A retrospective analysis of the clinicopathological data was performed, focusing on the impact of VI detected by routine H&E staining on disease-free survival (DFS) and cancer-specific survival (CSS). The presence of VI was detected in 13.9% of our cohort. The VI status was significantly correlated with the tumor size, infiltration depth, and TNM stage (P < 0.05). Patients with VI showed significantly lower DFS and CSS compared with patients without VI (P < 0.0001 for both). The subgroup analysis indicated that the presence of VI was a negative predictor of DFS in all TNM stages and a predictor of lower CSS only in stage I (P < 0.05 for all). A multivariate Cox proportional analysis identified VI as an independent predictor of CSS (P = 0.022). The presence of VI is a risk factor for recurrence and an independent predictor of poor survival in nonmetastatic GC after curative resection. The VI status should be considered to stratify with this group of GC patients for adjuvant treatment and more effective follow-up protocol.

Malignant gliomas belong to the most threatening tumor entities and are hallmarked by rapid proliferation, hypervascularization and an invasive growth pattern. The primary obstacle in surgical treatment lies in differentiation between healthy and pathological tissue at the tumor margins, where current visualization methods reach their limits. Here, we report on a novel technique (vascular dual intraoperative visualization approach - vDIVA) enabling visualization of different tumor zones (TZ I-III) on the basis of angiogenic hotspots. We investigated glioblastoma patients who underwent 5-ALA fluorescence-guided surgery with simultaneous intraoperative ICG fluorescence angiography. This vDIVA technique revealed hypervascularized areas which were further histologically investigated. Neuropathological assessments revealed tissue areas at the resection margins corresponding to TZ II, and postoperative CD34- and Map2 immunostaining confirmed these angiogenic hotspots to be occupied by glioma cells. Hence, the vascular architecture in this transitional zone could be well differentiated from both primary tumor bulk and healthy brain parenchyma. These data demonstrate that ICG fluorescence angiography improves state-of-the-art glioma surgery techniques and facilitates the future characterization of polyclonal attributes of malignant gliomas.

This systematic review examined whether the available evidence justifies using hepatic resection (HR) during later stages of hepatocellular carcinoma (HCC), which contravenes treatment guidelines but is current practice at many medical centers.Official guidelines and retrospective studies recommend different roles for HR for patients with large/multinodular HCC or with HCC involving macrovascular invasion (MVI).Several databases were systematically searched for studies examining the safety and efficacy of HR for treating HCC involving a single large tumor (>5 cm) or multiple tumors, or for treating HCC involving MVI.We identified 50 studies involving 14, 808 patients that investigated the use of HR to treat large/multinodular HCC, and 24 studies with 4389 patients that investigated HR to treat HCC with MVI. Median in-hospital mortality for patients with either type of HCC was significantly lower in Asian studies (2.7%) than in non-Asian studies (7.3%, P < 0.001). Median overall survival (OS) was significantly higher for all Asian patients with large/multinodular HCC than for all non-Asian patients at both 1 year (81% vs 65%, P < 0.001) and 5 years (42% vs 32%, P < 0.001). Similar results were obtained for median disease-free survival at 1 year (61% vs 50%, P < 0.001) and 5 years (26% vs 24%, P < 0.001). However, median OS was similar for Asian and non-Asian patients with HCC involving MVI at 1 year (50% vs 52%, P = 0.45) and 5 years (18% vs 14%, P = 0.94). There was an upward trend in 5-year OS in patients with either type of HCC.HR is reasonably safe and effective at treating large/multinodular HCC and HCC with MVI. The available evidence argues for expanding the indications for HR in official treatment guidelines.

Background: Diffuse dermal angiomatosis (DDA) is a rare skin condition considered to be a type of reactive angioendotheliomatosis. Histologic features are quite characteristic. It has been reported in association with vaso-occlusive disease, trauma, or underlying hypercoagulability. In the past, it was thought to be most common on the lower extremities., Objective: The purpose of this study was to describe the clinical and histologic features of 5 patients with DDA., Methods: The clinical and histologic features of 5 patients with DDA were evaluated., Results: Five women (47-58 years old) had DDA of the breast. Histologic examination showed a diffuse proliferation of benign endothelial cells between the collagen bundles throughout the dermis., Limitations: The main limitation of our study is the limited number of patients., Conclusion: Involvement of the breast is much more common than previously reported. Smoking seems to be a strong risk factor for the disease. Revascularization, oral corticosteroids, and oral anticoagulation have all been reported to be somewhat successful in the treatment of DDA of the breast., (Copyright © 2014 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

We describe the case of a 23-month-old female infant with a diagnosis of hemolytic uremic syndrome (HUS) and hemorrhagic retinopathy. The patient had a past history of abdominal pain, bloody diarrhea, and acute renal failure. On ophthalmologic examination, indirect ophthalmoscopy revealed extensive areas of flame-shaped hemorrhage, cotton wool spots, macular edema and optic nerve head neovascularization in both eyes. Fluorescein angiography showed severe bilateral retinal ischemia and neovascularization leakage in disk. The patient, who had the visual acuity of 20/1000 in the right eye (OD) and 20/540 in the left eye (OS) at the first examination, was treated with panretinal photocoagulation (PRP) and presented at the end of the 6th month of follow-up improvement to 20/540 in OD and 20/270 in OS. There was also a regression of disc neovascularization, hemorrhages and macular edema. Despite intense retinal ischemia, there were no complications related to angiogenesis such as vitreous hemorrhage and/or neovascular glaucoma. We describe, in this report, the association between hemorrhagic retinopathy with features of Purtscher-like disease and HUS.

Purpose: To investigate whether the prophylactic use of bevacizumab reduces the rate of rubeosis after proton therapy for uveal melanoma and improves the possibility to treat ischemic, reapplicated retina with laser photocoagulation., Design: Comparative retrospective case series., Methods: Uveal melanoma patients with ischemic retinal detachment and treated with proton therapy were included in this institutional study. Twenty-four eyes received prophylactic intravitreal bevacizumab injections and were compared with a control group of 44 eyes without bevacizumab treatment. Bevacizumab injections were performed at the time of tantalum clip insertion and were repeated every 2 months during 6 months, and every 3 months thereafter. Ultra-widefield angiography allowed determination of the extent of retinal ischemia, which was treated with laser photocoagulation after retinal reapplication. Main outcome measures were the time to rubeosis, the time to retinal reattachment, and the time to laser photocoagulation of ischemic retina., Results: Baseline characteristics were balanced between the groups, except for thicker tumors and larger retinal detachments in the bevacizumab group, potentially to the disadvantage of the study group. Nevertheless, bevacizumab prophylaxis significantly reduced the rate of iris rubeosis from 36% to 4% (log-rank test P = .02) and tended to shorten the time to retinal reapplication until laser photocoagulation of the nonperfusion areas could be performed., Conclusions: Prophylactic intravitreal bevacizumab in patients treated with proton therapy for uveal melanoma with ischemic retinal detachment prevented anterior segment neovascularization, until laser photocoagulation to the reapplied retina could be performed., (Copyright © 2014 Elsevier Inc. All rights reserved.)

We present the sonographic and magnetic resonance imaging findings of Leydig cell tumors in a series of patients, along with a brief review of the literature. We evaluated the sonographic features of 11 cases of Leydig cell tumors, including echogenicity, size, margins, and patterns of vascularity. The magnetic resonance imaging characteristics of 9 patients were also assessed, with special attention to the appearance of the tumors on T2-weighted imaging and postcontrast T1-weighted imaging. Seven tumors were hypoechoic, and 4 were almost isoechoic. Ten patients showed various patterns of hypervascularity in the tumors, combined in some cases with feeding vessels. One case presented with a single feeding vessel. The tumors showed homogeneous or heterogeneous low signal intensity on T2-weighted imaging and marked enhancement on postcontrast T1-weighted imaging. The small size of these tumors, the various patterns of vascularity on color and power Doppler sonography, and the marked enhancement on postcontrast T1-weighted imaging are considered valuable but generally nonspecific for identification of these tumors., (© 2014 by the American Institute of Ultrasound in Medicine.)

To determine the optimal area of retinal photocoagulation required for suppressing active neovascularisation (NVI) associated with diabetic retinopathy. We studied 1 eye each of 4 patients in whom active NVI was ophthalmoscopically shown to have been suppressed by additional photocoagulation. These patients initially underwent pan-retinal photocoagulation for diabetic retinopathy at another hospital, but NVI developed subsequently. We compared the areas of photocoagulation before and after additional photocoagulation and compared the area of retinal photocoagulation. The photocoagulated areas before and after additional photocoagulation in the four eyes were 20.7 and 45.2, 36.6 and 56.3, 30.4 and 67.4, and 11.7 and 53.4 %, respectively. The area of retinal photocoagulation required to suppress active NVI is calculated to be ~50 %.

Purpose: To evaluate the feasibility of arterial spin-labeling (ASL) in head and neck cancer for noninvasive measurement of tumor blood flow (TBF), by comparing 1) the TBF change before and after the treatment, and 2) posttreatment TBF and its reduction rate between residual and nonresidual tumors after treatment., Materials and Methods: Twenty-two patients with head and neck cancer were evaluated using ASL on 3.0-T magnetic resonance imaging (MRI) before and after nonsurgical treatment. A pulsed ASL sequence with Look–Locker readout was used to calculate quantitative TBF. TBF reduction rates between pre- and posttreatment values were also calculated. Residual tumors were confirmed when present with either histopathologically or clinical follow-up., Results: Pre- and posttreatment mean TBF values were 121.4 ± 27.8 (standard deviation) and 24.9 ± 14.9 mL/100g/min, respectively. Pre- and posttreatment TBF differed significantly. Posttreatment TBF was significantly higher in patients with residual tumors (five patients, 46.9 ± 7.1 mL/100g/min) than in those without (17 patients, 18.4 ± 9.2 mL/100g/min). The TBF reduction rate was significantly lower in patients with residual tumors (0.540.55 ± 0.120.12) than in those without (0.85 ± 0.06)., Conclusion: ASL allows quantitative assessment of TBF in head and neck cancer. ASL may be useful for noninvasive assessment of tumor viability in head and neck cancer.

Background and Objective: Fractional CO2 laser has recently emerged as a promising therapeutic modality to improve the texture and appearance of burn scars. An issue in many burn scars is persistent erythema, which traditionally has been treated with vascular lasers. Interestingly, fractional CO2 lasers have been shown to improve the appearance of burn scars, including erythema, but no mechanism has been proposed for this change. Our objective is to evaluate the histopathologic changes in vasculature in burn scars treated with fractionated CO2 laser, and to attempt to describe the mechanism behind reduced erythema following treatment., Study Design/materials and Methods: Uncontrolled, prospective study of ten patients with mature burn scars, from a clinical and histological perspective. Biopsy specimens were obtained before and 2 months after 3 treatment sessions. Anti-CD31 immunostaining was performed to highlight vascular patterns in biopsy specimens., Results: In histological analysis, an increase in vascular density, particularly of small caliber vessels, was seen following treatment, with an 82.6% average increase in vasculature (P = 0.028). This increase in vascularity correlated with a decrease in clinical erythema and vascularity scores, measured using the Vancouver Scar Scale., Conclusion: Mature hypertrophic burn scars treated with a fractional CO2 laser showed a statistically significant increase in vascular density in the superficial dermis. A non-statistical decrease in clinically perceived erythema and improvement of overall appearance was seen. To our knowledge, this is the first report of increased vascular density in burn scars treated with fractional CO2 laser and suggests our prior assumptions on causes of erythema in mature hypertrophic scars may need to be challenged., (© 2014 Wiley Periodicals, Inc.)

Purpose: To determine the 1-year and 2-year likelihood of vitrectomy in diabetic patients undergoing initial pan retinal photocoagulation (PRP)., Methods: Diabetic eyes receiving initial PRP for proliferative diabetic retinopathy (PDR) were analyzed to determine their risk for vitrectomy based on clinical findings., Results: In total, 374 eyes of 272 patients were analyzed. The percentage of eyes undergoing vitrectomy 1 year and 2 years following initial PRP was 19.1% and 26.2%, respectively. Of the eyes in Group 1 (PDR alone), Group 2 (PDR and vitreous hemorrhage), and Group 3 (PDR and iris neovascularization, vitreous hemorrhage with traction or fibrosis, or fibrosis alone), the percentage receiving pars plana vitrectomy at 1 year and 2 years was 9.73% (18/185) and 15.7% (29/185), 26.9% (43/160) and 34.4% (55/160), and 37.9% (11/29) and 48.3% (14/29), respectively. Eyes in Group 2 had 2.78 times greater likelihood (P < 0.0001) and eyes in Group 3 had 3.54 times higher likelihood (P < 0.0001) of requiring pars plana vitrectomy within 2 years than those with PDR alone., Conclusion: Eyes receiving PRP for PDR with associated hemorrhage or traction were more likely to undergo pars plana vitrectomy within 1 year and 2 years following initial PRP compared with eyes with only PDR, providing important prognostic information for PRP-naive patients.

Objective: The objective of our study was to prospectively investigate whether nonsmooth margins detected on multiphasic CT images correlate with the presence and location of microvascular invasion (MVI) in hepatocellular carcinoma (HCC)., Subjects and Methods: A total of 102 patients with preoperative CT findings of solitary HCC were prospectively enrolled. Tumor size, tumor capsule, tumor margins, and peritumoral enhancement on preoperative CT images were assessed. Histopathologic results including the following were also recorded: tumor differentiation; liver fibrosis score; presence or absence of MVI; and, if present, the location of MVI. Correlation between tumor margin on preoperative CT images and histopathologic location of MVI was determined., Results: Pathologic examination revealed MVI in 60 of the 102 HCC specimens. Although the results of the univariate analysis showed that tumor size, higher Edmondson-Steiner grade, and nonsmooth tumor margins were associated with MVI, multivariate analysis revealed that only nonsmooth margins correlated with the presence of MVI in HCC (p < 0.001). Of the 60 HCC specimens with histopathologic evidence of MVI, 40 exhibited focal nonsmooth margins. In addition, the locations of the nonsmooth margins and MVI were similar in 36 of the 40 specimens., Conclusion: Nonsmooth tumor margins correlated with the histopathologic presence and location of MVI. Therefore, nonsmooth margins detected on multiphasic CT may be predictive of MVI in HCC.

We performed this study to examine the prevalence of tumor deposits (TD) in gastric adenocarcinomas (GACa), and the relevance of their presence, size and type to clinical outcome. Ninety-six patients, histopathologically diagnosed as GACa following a total/subtotal gastrectomy were included, and clinicopathologic data were recorded. Due to the statistical analysis, the majority of TD(+) cases were of intestinal type and showed vascular invasion. In these cases, the incidence of local recurrence was significantly higher. The majority of GACa of intestinal type with TD were of high grade and showed vascular invasion. Recurrence and death were more commonly encountered among them. The recurrence-free survival (RFS) was significantly shorter in patients with TDs, which was also confirmed by multivariate analysis, and there was a significant difference between both RFS and overall survival of TD(+) and TD(-) cases of intestinal type GACa. In conclusion, in this study, we demonstrate that TDs are not infrequently observed in GACa, they are more commonly associated with the intestinal type and vascular invasive gastric cancers. Our study shows the prognostic impact of TDs, especially regarding the RFS. Therefore, the documentation of TDs might be considered for prospective studies, especially for the intestinal type GACa, a shortcoming of this study., (Copyright © 2014 Elsevier GmbH. All rights reserved.)

Background: Irreversible electroporation (IRE) has recently been added as an additional therapeutic ablative option in patients with locally advanced cancers (LAC) involving vital structures. IRE delivers localized electric current by peri-tumoral discrete probes to attain irreversible changes in cell membrane leading to cell death. The aim of this study was to evaluate the long-term effects of IRE in the treatment of locally advanced tumors., Methods: A prospective IRB approved evaluation of 107 consecutive patients from 7 institutions with tumors that had vascular invasion treated with IRE from 5/2010 to 1/2012. LAC was defined as primary tumor with <5 mm from major vascular structure based on pre-operative dynamic imaging or intra-operative criteria., Results: IRE as utilized in LAC in the liver (N = 42, 40%) and pancreas (N = 37, 35%), with a median number of lesions being 2 with a mean target size of 3 cm. IRE attributable morbidity rate was 13.3% (total 29.3%) with high-grade complications seen in 4.19% (total 12.6%). No significant vascular complications were seen, and of the high-grade complications, bleeding (2), biliary complications (3) and DVT/PE (3) were the most common. Complications were more likely with pancreatic lesions (p = 0.0001) and open surgery (p = 0.001). Calculated local recurrence free survival (LRFS) was 12.7 months with a median follow up of 26 months censured at last follow up. The tumor target size was inversely associated with recurrence free survival (b = 0.81, 95% CI: 1.6 to 4.7, p value = 0.02) but this did not have a significant overall survival impact., Conclusions: IRE represents a novel therapeutic option in patients with LAC involving vital structures that are not amenable to surgical resection. Acceptable to high local disease control and the long LRFS can be achieved with this therapy in combination with other multi-disciplinary therapies.

Bone marrow mononuclear cells (BMMNCs) are important for angiogenesis after stroke. We investigated the effects of BMMNCs on cognitive function, angiogenesis, and the vascular endothelial growth factor (VEGF)-VEGF receptor 2 (VEGFR2) signaling pathway in a rat model of vascular dementia. We transplanted BMMNCs into rats that had undergone permanent bilateral occlusion of the common carotid arteries (2VO) and observed their migration in vivo. On day 28, we assessed cognitive function with the Morris Water Maze test and examined vascular density and white matter damage within the corpus striatum by staining with fluorescein lycopersicon esculentum (tomato) lectin or Luxol fast blue. We evaluated expression of VEGF, rapidly accelerated fibrosarcoma 1 (Raf1), and extracellular-signal-regulated kinases 1 and 2 (ERK1/2) in the ischemic hemisphere by Western blot analysis on day 7 after cell transplantation. Contribution of the VEGF-VEGFR2 signaling pathway was confirmed by using VEGFR2 inhibitor SU5416. BMMNCs penetrated the blood-brain barrier and reached the ischemic cortex and white matter or incorporated into vascular walls of 2VO rats. BMMNC-treated 2VO rats had better learning and memory, higher vascular density, and less white matter damage than did vehicle-treated rats. The beneficial effects of BMMNCs were abolished by pretreatment of rats with SU5416. Protein expression of VEGF and phosphorylated Raf1 and ERK1/2 was also significantly increased by BMMNC treatment, but this upregulation was reversed by SU5416. BMMNCs can enhance angiogenesis, reduce white matter damage, and promote cognitive recovery in 2VO rats. The angiogenic effect may result from upregulation of the VEGF-VEGFR2 signaling pathway., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: Surgical therapies are the first-line treatments for hepatocellular carcinoma (HCC) patients. However, the high incidence of tumor metastasis after liver surgery remains a severe problem. We aim to investigate the roles and the underlying mechanism of YQ23, stabilized non-polymeric diaspirin cross-linked tetrameric hemoglobin, in liver tumor metastasis after major hepatectomy and partial hepatic ischemia reperfusion (I/R) injury., Methods: An orthotopic liver tumor model in Buffalo rat was established using the hepatocellular carcinoma cell line McA-RH7777. Major hepatectomy for tumor-bearing lobe and partial hepatic I/R injury were performed at two weeks after orthotopic liver tumor implantation. YQ23 (0.2 g/kg) was administered at 1 hour before ischemia and immediately after reperfusion. Blood samples were collected at day 0, 1, 7, 14, 21 and 28 for detection of circulating endothelial progenitor cells (EPCs) and regulatory T cells (Tregs)., Results: Our results showed that YQ23 treatment effectively inhibited intrahepatic and lung metastases together with less tumor angiogenesis at 4 weeks after major hepatectomy and partial hepatic I/R injury. The levels of circulating EPCs and Tregs were significantly decreased in YQ23 treatment group. Furthermore, YQ23 treatment also increased liver tissue oxygenation during hepatic I/R injury. Up-regulation of HO1 and down-regulation of CXCR3, TNF-α and IL6 were detected after YQ23 treatment., Conclusions: YQ23 treatment suppressed liver tumor metastasis after major hepatectomy and partial hepatic I/R injury in a rat liver tumor model through increasing liver oxygen and reducing the populations of circulating EPCs and Tregs.

Purpose: The aims of this study were to determine the scleral attenuation of focused neodymium: yttrium-lanthanum-fluoride laser at 1,047 nm applied transsclerally and whether transscleral delivery can close the vascular supply at the base of experimental choroidal melanoma in rabbits., Methods: Fifty-two New Zealand albino rabbits were included. Scleral laser attenuation was measured across fresh sclera. B16F10 melanomas were established in the subchoroidal space of 49 rabbits. Twenty-one animals were killed immediately after transscleral treatment, 14 were followed for 2 weeks to 4 weeks, and 14 were followed without treatment. Ophthalmoscopy, fundus photographs, and fluorescein angiography were performed before treatment, immediately after, and weekly during the follow-up. Eyes were examined by light microscopy., Results: Sclera attenuated laser energy by 31% ± 7%. Immediately after treatment, angiography showed diffuse hypofluorescence in 71% (15 of 21 rabbits). Light microscopy showed vascular occlusion extending at least two thirds of the tumor thickness from the base. Seven of the 14 tumors followed for 15 days ± 8 days were eradicated. There was no correlation between tumor height and eradication., Conclusion: Rabbit sclera attenuated 31% ± 7% of laser energy. A single transscleral treatment causes tumor vascular closure at the base and may serve as an adjuvant therapy to ensure destruction of deep and intrascleral tumor cells.

Objective: The purpose of this article is to prospectively and directly compare the capabilities of non-contrast-enhanced MR angiography (MRA), 4D contrast-enhanced MRA, and contrast-enhanced MDCT for assessing pulmonary vasculature in patients with non-small cell lung cancer (NSCLC) before surgical treatment., Subjects and Methods: A total of 77 consecutive patients (41 men and 36 women; mean age, 71 years) with pathologically proven and clinically assessed stage I NSCLC underwent thin-section contrast-enhanced MDCT, non-contrast-enhanced and contrast-enhanced MRA, and surgical treatment. The capability for anomaly assessment of the three methods was independently evaluated by two reviewers using a 5-point visual scoring system, and final assessment for each patient was made by consensus of the two readers. Interobserver agreement for pulmonary arterial and venous assessment was evaluated with the kappa statistic. Then, sensitivity, specificity, and accuracy for the detection of anomalies were directly compared among the three methods by use of the McNemar test., Results: Interobserver agreement for pulmonary artery and vein assessment was substantial or almost perfect (κ=0.72-0.86). For pulmonary arterial and venous variation assessment, there were no significant differences in sensitivity, specificity, and accuracy among non-contrast-enhanced MRA (pulmonary arteries: sensitivity, 77.1%; specificity, 97.4%; accuracy, 87.7%; pulmonary veins: sensitivity, 50%; specificity, 98.5%; accuracy, 93.2%), 4D contrast-enhanced MRA (pulmonary arteries: sensitivity, 77.1%; specificity, 97.4%; accuracy, 87.7%; pulmonary veins: sensitivity, 62.5%; specificity, 100.0%; accuracy, 95.9%), and thin-section contrast-enhanced MDCT (pulmonary arteries: sensitivity, 91.4%; specificity, 89.5%; accuracy, 90.4%; pulmonary veins: sensitivity, 50%; specificity, 100.0%; accuracy, 95.9%) (p>0.05)., Conclusion: Pulmonary vascular assessment of patients with NSCLC before surgical resection by non-contrast-enhanced MRA can be considered equivalent to that by 4D contrast-enhanced MRA and contrast-enhanced MDCT.

Objective: To evaluate the effects of mast cell count and angiogenesis on the prognosis of renal cell carcinoma., Methods: The retrospective study was conducted at the Harran University, Sanliurfa, Turkey, and included 64 cases with diagnosis of renal cell carcinoma between 2002 and 2012. Immunohistochemical analysis was performed on paraffin sections using the standard streptavidin-biotin immunoperoxidase method. CD31 antibodies were used to identify microvessels in tumoural tissues. The microvessel density was calculated using a serological method. The mean vascular density was equivalent to the vascular surface area (in mm2) per unit tissue volume (in mm3) (MVD = mm3). Mast cells tryptase antibody was used to evaluate the mast cell count in tumoural and non-tumoural tissues. The relationship between mast cell count and microvessel density was evaluated and compared with stage, grade, tumour diameter, and age., Results: The mast cell count in the tumoral tissue of renal cell carcinoma was significantly higher compared with non-neoplastic renal tissue (p < 0.001). A significant relationship was found between the mast cell count in tumoral tissue and stage, grade, and tumour diameter (p < 0.001). However, no relation was found with age (p > 0.05). The intratumoural mast cell count in clear cell renal carcinoma was significantly higher compared with non-clear variety (p = 0.001). No significant relationship was found between microvessel density, age, stage, diameter, or grade of the tumour and tumoral mast cell count (p > 0.05)., Conclusion: No significant association was found between the number of mast cells in tumoral tissue and microvessel density. Further studies are needed to demonstrate the effect of mast cells on angiogenesis in renal cell carcinoma.

Background: Pulmonary capillary hemangiomatosis (PCH) is a rare disease of capillary proliferation of unknown cause and with a high mortality. Families with multiple affected individuals with PCH suggest a heritable cause although the genetic etiology remains unknown., Methods: We used exome sequencing to identify a candidate gene for PCH in a family with two affected brothers. We then screened 11 unrelated patients with familial (n = 1) or sporadic (n = 10) PCH for mutations., Results: Using exome sequencing, we identified compound mutations in eukaryotic translation initiation factor 2 α kinase 4 (EIF2AK4) (formerly known as GCN2) in both affected brothers. Both parents and an unaffected sister were heterozygous carriers. In addition, we identified two EIF2AK4 mutations in each of two of 10 unrelated individuals with sporadic PCH. EIF2AK4 belongs to a family of kinases that regulate angiogenesis in response to cellular stress., Conclusions: Mutations in EIF2AK4 are likely to cause autosomal-recessive PCH in familial and some nonfamilial cases.

Peripheral arterial disease is a common manifestation of systemic atherosclerosis, which results in more serious consequences of ischemic events in peripheral tissues such as the lower extremities. Cell therapy has been tested as a treatment for peripheral ischemia that functions by inducing angiogenesis in the ischemic region. However, the poor survival and engraftment of transplanted cells limit the efficacy of cell therapy. In order to overcome such challenges, we applied genetically engineered cell sheets using a cell-interactive and thermosensitive hydrogel and nonviral polymer nanoparticles. C2C12 myoblast sheets were formed on Tetronic-tyramine (Tet-TA)-RGD hydrogel prepared through a highly efficient and noncytotoxic enzymatic reaction. The myoblast sheets were then transfected with vascular endothelial growth factor (VEGF) plasmids using poly(β-amino ester) nanoparticles to increase the angiogenic potential of the sheets. The transfection increased the VEGF expression and secretion from the C2C12 sheets. The enhanced angiogenic effect of the VEGF-transfected C2C12 sheets was confirmed using an in vitro capillary formation assay. More importantly, the transplantation of the VEGF-transfected C2C12 sheets promoted the formation of capillaries and arterioles in ischemic muscles, attenuated the muscle necrosis and fibrosis progressed by ischemia, and eventually prevented ischemic limb loss. In conclusion, the combination of cell sheet engineering and genetic modification can provide more effective treatment for therapeutic angiogenesis.

Background and Aim: Long-term data after liver resection for hepatocellular carcinoma (HCC) with vascular invasion are rare for non-Asian patients. The aim of the present study was to analyze the long-term outcome of liver resection for HCC with vascular invasion and to compare the results of subgroups with micro- and macrovascular invasion., Methods: From January 2000 to September 2010, 288 patients without extrahepatic metastases underwent liver resection for HCC. In 107 out of 288 patients (37%), vascular invasion was found in the final pathological analysis. The long-term outcome as well as the perioperative course of these patients was analyzed using a prospective database., Results: The 1-, 3- and 5-year cumulative survival rate of HCC patients with vascular invasion was 64.3, 41.4 and 23.9%, respectively. The median survival was 19 months. In the multivariate analysis, the overall survival was not influenced by the type of vascular invasion (micro- vs. macrovascular invasion), however overall survival was significantly impaired in case of lymphatic vessel invasion, intraoperative blood transfusions, need of fresh frozen plasma application, prolonged ICU stay and elevated preoperative bilirubin levels., Conclusions: Acceptable survival rates can be achieved in selected patients with macrovascular invasion after surgical resection, which is not markedly different from those with microvascular invasion. In view of an otherwise poor prognosis, liver resection seems to be justified for selected HCC patients with macrovascular invasion, although this stands in contrast with the BCLC recommendations. However, it is in accordance for example with the guidelines of the Asia-Pacific Association for the Study of the Liver.

Objective: The purpose of this study is to evaluate the CT appearances of tumor responses following hypofractionated stereotactic ablative body radiotherapy for small hypervascular hepatocellular carcinomas (HCCs) and to assess the relationship between tumor responses and local control., Materials and Methods: Among 277 HCC tumors treated with stereotactic ablative body radiotherapy (35 or 40 Gy per five fractions), we selected enhanced lesions on arterial phase CT performed before stereotactic ablative body radiotherapy. Radiographic findings after stereotactic ablative body radiotherapy were evaluated during a 2-year follow-up period with the modified Response Evaluation Criteria in Solid Tumors. Local control and survival rates were calculated with the Kaplan-Meier method., Results: Forty-two tumors with a median size of 2.1 cm (range, 1.0-3.8 cm) were selected with a median follow-up of 23.3 months (range, 9-56 months). Local recurrence was observed in two tumors after achieving a complete response (CR). The 2-year local control rate was 97%, and the overall survival rate was 81%. CR increased from 10 (24%) to 28 (67%) to 30 (71%) tumors at 3, 6, and 12 months after stereotactic ablative body radiotherapy. Overall CR at maximum follow-up was 39 tumors (93%), yet three enhanced tumors persisted for more than 2 years. The median time to achieve CR was 5.9 months (range, 1.2-34.2 months)., Conclusion: The CR rate in hypervascular HCCs after hypofractionated stereotactic ablative body radiotherapy increased during the 2-year follow-up period. Cautious and continuous observation until tumor regrowth is considered relevant to evaluate a true effect of this treatment. Further studies for the optimal evaluation of treatment outcome after stereotactic ablative body radiotherapy are warranted.

The myoma pseudocapsule (MP) is a fibro-vascular network rich of neurotransmitters, as a neurovascular bundle, surrounding fibroid and separating myoma from myometrium. We investigated the distribution of the opioid neuropeptides, as enkephalin (ENK) and oxytocin (OXT), in the nerve fibers within MP and their possible influence in human reproduction in 57 women. An histological and immunofluorescent staining of OXT and ENK was performed on nerve fibers of MP samples from the fundus, corpus and isthmian-cervical regions, with a successive morphometric quantification of OXT and ENK. None of the nerve fibers in the uterine fundus and corpus MPs contained ENK and the nerve fibers in the isthmian-cervical region demonstrated an ENK value of up to 94 ± 0.7 CU. A comparatively lower number of OXT-positive nerve fibers were found in the fundal MP (6.3 ± 0.8 CU). OXT-positive nerve fibers with OXT were marginally increased in corporal MP (15.0 ± 1.4 CU) and were substantially higher in the isthmian-cervical region MP (72.1 ± 5.1 CU) (p < 0.01). The distribution of OXY neurofibers showed a slight into the uterine corpus, while are highly present into the cervico-isthmic area, with influence on reproductive system and sexual disorders manifesting after surgical procedures on the cervix.

Objective: The aim of this study is to reveal inhibitory effect of gamma knife irradiation on angiogenesis of meningiomas using rat corneal angiogenesis assay., Methods: A total of 72 rats were divided into three preliminary groups. Each group, consisting of 24 rats, was implanted to World Health Organization (WHO) grade I (typical), grade II (atypical), and grade III (malignant) meningioma. Each of these three preliminary groups of 24 rats, were then divided into four subgroups, each consisting of 6 rats and subsequently irradiated by gamma knife with dose prescriptions of 0, 14, 18, and 22 Gy. The numbers of vessels that developed around the micropockets of the corneas were counted and photographed on days 5, 10, 15, and 20., Results: For WHO grade I meningiomas, 18 and 22 Gy doses (P < 0.001), and for grade II meningiomas, the 22-Gy (P = 0.021) dose were found to inhibit tumor-induced angiogenesis compared with the radiation-free control group. For grade III meningiomas, there was no statistical difference with the control group in any of the doses applied. Our findings demonstrate that gamma knife irradiation may suppress the angiogenic activity of WHO grades I and II meningiomas but not of the grade III meningiomas., Conclusions: For the first time, this study provides an experimental data to show the antiangiogenic effect of gamma knife irradiation on meningiomas., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Cell-mediated angiogenic therapy for ischemic heart disease has had disappointing results. The lack of clinical translatability may be secondary to cell death and systemic dispersion with cell injection. We propose a novel tissue-engineered therapy, whereby extracellular matrix scaffold seeded with endothelial progenitor cells (EPCs) can overcome these limitations using an environment in which the cells can thrive, enabling an insult-free myocardial cell delivery to normalize myocardial biomechanics., Methods and Results: EPCs were isolated from the long bones of Wistar rat bone marrow. The cells were cultured for 7 days in media or seeded at a density of 5 × 10(6) cells/cm(2) on a collagen/vitronectin matrix. Seeded EPCs underwent ex vivo modification with stromal cell-derived factor-1α (100 ng/mL) to potentiate angiogenic properties and enhance paracrine qualities before construct formation. Scanning electron microscopy and confocal imaging confirmed EPC-matrix adhesion. In vitro vasculogenic potential was assessed by quantifying EPC cell migration and vascular differentiation. There was a marked increase in vasculogenesis in vitro as measured by angiogenesis assay (8 versus 0 vessels/hpf; P=0.004). The construct was then implanted onto ischemic myocardium in a rat model of acute myocardial infarction. Confocal microscopy demonstrated a significant migration of EPCs from the construct to the myocardium, suggesting a direct angiogenic effect. Myocardial biomechanical properties were uniaxially quantified by elastic modulus at 5% to 20% strain. Myocardial elasticity normalized after implant of our tissue-engineered construct (239 kPa versus normal=193, P=0.1; versus infarct=304 kPa, P=0.01)., Conclusions: We demonstrate restoration and normalization of post-myocardial infarction ventricular biomechanics after therapy with an angiogenic tissue-engineered EPC construct.

Introduction: The results of surgical outcomes of 20 gauge pars plana vitrectomy in Eales' disease are available in the scientific literature. However, all these studies have been done using the 20 gauge vitrectomy systems and most studies have been conducted in a retrospective manner., Objective: To evaluate the outcomes and safety of 23 gauge vitrectomy in complications of Eales' disease., Study Design: Consecutive interventional case series., Participants: Seventy-six eyes of 72 nonconsecutive patients undergoing 23-gauge vitrectomy for complications of Eales' disease were enrolled. The participants were followed up for a minimum of one year., Intervention: The participants underwent a complete demographic, medical and ophthalmic evaluation. A 23-gauge vitrectomy was performed. Endotamponade was used when necessary. Perioperative and postoperative events were recorded. Primary outcome measures were visual acuity and complications arising due to surgery., Results: Indication for surgery was non-clearing vitreous hemorrhage in 89.4% (68/76) and secondary retinal detachment in 10.6% (8). Visual acuity improved from Log Mar 1.80 ± 0.19 units preoperatively to Log Mar 0.47±0.59. Best-corrected visual acuity equivalent to Snellen 6/9 was achieved in 77. 6% of eyes. . Surgical failure was seen in 6.5% cases. Four cases were lost due to progression to neovascular glaucoma and 1 case was lost to severe residual retinal detachment. Iatrogenic portside retinal breaks occurred in 3.9% (3), post-vitrectomy retinal detachment 2.6% ( 2), hypotony 1.3% (1) and cataract in 38.1% (28) cases., Conclusion: 23-gauge sutureless vitrectomy in patients with Eales' disease is a safe and effective technique with acceptable level of risk and complications., (© NEPjOPH.)

The development of anti-vascular endothelial growth factor (VEGF) molecules has expanded the range of available treatment options for many ocular diseases, including neovascular glaucoma (NVG). A number of studies have explored the use of anti-VEGF agents as stand-alone or adjunctive treatment for NVG. Although no large, prospective, randomized trials have been performed to date, the growing body of knowledge suggests that anti-VEGF agents are effective at reversing iris and angle neovascularization and lowering intraocular pressure in patients with NVG. Response to a single injection is typically temporary; therefore, laser or incisional surgery is still necessary in most cases. Future research is needed to determine the optimal agent, dose, route of administration, and timing of treatment either as monotherapy or coupled with other medical and/or surgical interventions.

Object: There have been significant advances in understanding the angioarchitecture of spinal dural arteriovenous fistulas (AVFs). However, the major intradural retrograde venous drainage system has not been investigated in detail, including the most proximal sites of intradural radiculomedullary veins as they connect to the dura mater, which are the final targets of interruption in both microsurgical and endovascular treatments., Methods: Between April 1984 and March 2011, 27 patients with 28 AVFs were treated for spinal dural AVFs at the authors' university hospital. The authors assessed vertebral levels of feeding arteries and dural AVFs by using conventional digital subtraction angiography. They also assessed 3D locations of the most proximal sites of intradural radiculomedullary veins and the 3D positional relationship between the major intradural retrograde venous drainage system and intradural neural structures, including the spinal cord, spinal nerves, and the artery of Adamkiewicz, by using operative video recordings plus 3D rotational angiography and/or 3D computer graphics. In addition, they statistically assessed the clinical results of 27 cases. Of these lesions, 23 were treated with open microsurgery and the rest were treated with endovascular methods., Results: Feeding arteries consisted of T2-10 intercostal arteries with 19 lesions, T-12 subcostal arteries with 3 lesions, and L1-3 lumbar arteries with 6 lesions. The 3D locations of the targets of interruption (the most proximal sites of intradural radiculomedullary veins as they connect to the dura mater) were identified at the dorsolateral portion of the dura mater adjacent to dorsal roots in all 19 thoracic lesions, whereas they were identified at the ventrolateral portion of the dura mater adjacent to ventral roots in 7 (78%) of 9 cases of conus medullaris/lumbar lesions (p < 0.001). The major intradural retrograde venous drainage system was located dorsal to the spinal cord in all 19 thoracic lesions, whereas it was located ventral to the spinal cord in 4 (44%) of 9 cases of conus/lumbar lesions (p = 0.006). In 3 (11%) of 27 cases, AVFs had a common origin of the artery of Adamkiewicz. In 2 lumbar lesions, the artery of Adamkiewicz ascended very close to the vein because of its ventral location. Although all lesions were successfully obliterated without major complications and both gait and micturition status significantly improved (p = 0.005 and p = 0.015, respectively), conus/lumbar lesions needed careful differential diagnosis from ventral intradural perimedullary AVFs, because the ventral location of these lesions contradicted the Spetzler classification system., Conclusions: The angioarchitecture of spinal dural AVFs in the thoracic region is strikingly different from that in conus/lumbar regions with regard to the intradural retrograde venous drainage system. One should keep in mind that spinal dural AVFs are not always dorsal types, especially in conus/lumbar regions.

Background: The objective of this study was comparison of characteristics of the microvasculature in transition zone tumor (TZT) and benign nodular hyperplasia (BPH) with normal prostatic transition zone (NTZ), applying accurate and objective quantification based on digital image analysis. Results of this study may increase understanding of prostate dynamic contrast enhanced (DCE) MRI analysis., Methods: Radical prostatectomy specimens of 28 patients containing TZT ranging from pT2-pT4 were used. In 11 patients a concomitant peripheral zone tumor (PZT) was present. Microvessels were visualized by CD31 immunohistochemistry. Specimens were scanned using a computer-controlled microscope with automatic recognition of microvessels. Pseudocolor maps were produced displaying microvessel density, perimeter, and area of an entire prostate transection. Mean, 75th percentile (p75) and coefficient of variation (CV) were calculated automatically in manually indicated areas of the tumor and corresponding contralateral normal tissue, and BPH., Results: Large variability was seen in TZT microvascular parameters, indicating presence of patients having both hypo and hypervascularized tumors compared to NTZ. In contrast, areas of BPH showed a more consistent increase in vascular parameters, with decreased CV. Analysis of PZT confirmed results of our previous study, with mean and p75 of all vascular parameters being significantly increased and a decrease in CV. No correlation was found for clinicopathological parameters and microvascular parameters., Conclusion: Microvasculature of transition zone tumor showed increased heterogeneity compared to BPH and peripheral zone tumors, possibly explaining the difficulty of TZT detection on DCE-MRI., (Copyright © 2012 Wiley Periodicals, Inc.)

Aim: To assess the feasibility of an unenhanced, flow-sensitive, alternating inversion recovery-balanced steady-state free precession (FAIR TrueFISP) arterial spin labelling (ASL) magnetic resonance imaging (MRI) technique for quantification of breast cancer perfusion., Materials and Methods: Eighteen untreated breast tumour patients (mean age 53 ± 17 years, range 30-68 years) and four healthy controls (mean age 51 ± 14 years, range 33-68 years) were enrolled in this study and were imaged using a clinical 1.5 T MRI machine. Perfusion measurements were performed using a coronal single-section ASL FAIR TrueFISP technique in addition to a routine breast MRI examination. T1 relaxation time of normal breast parenchyma was determined in four healthy volunteers using the variable flip angle approach. The definitive diagnosis was obtained at histology after biopsy or surgery and was available for all patients., Results: ASL perfusion was successfully acquired in 13 of 18 tumour patients and in all healthy controls. The mean ASL perfusion of invasive ductal carcinoma tissue was significantly higher (88.2 ± 39.5 ml/100 g/min) compared to ASL perfusion of normal breast parenchyma (24.9 ± 12.7 ml/100 g/min; p < 0.05) and invasive lobular carcinoma (30.5 ± 4.3 ml/100 g/min; p < 0.05). No significant difference was found between the mean ASL perfusion of normal breast parenchyma and invasive lobular carcinoma tissue (p = 0.97)., Conclusion: ASL MRI enables quantification of breast cancer perfusion without the use of contrast material. However, its impact on diagnosis and therapy management of breast tumours has to be evaluated in larger patient studies., (Copyright © 2012 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Background and Purpose: Optimal surgical resection improves the prognosis of glioblastomas. However, this goal is far from being achieved due to its invasive nature. Several studies have already shown the efficacy of fluorescence-guided surgery, in improving the quality of resection of glioblastoma. We report herein our experience through a retrospective serie and describe the principles, limitations and advantages of this technique., Methods: Between 2006 and 2009, 22 patients underwent resection of a glioblastoma guided by fluorescence. Following operations, all patients underwent sequential clinical examination and radiological monitoring using multimodal MRI. The extent of resection was assessed by the surgeon during the procedure and by the radiologist on MRI. The curves of progression-free clinical survival (SSP) and overall survival (SG) were analyzed. The prognostic value of the extent of resection was studied., Results: We obtained 68.2% of complete resection according to the absence of residual fluorescence as assessed by the surgeon, and 75% according to the absence of residual tumor on early MRI. The median SSP was 10.75 months and the median SG was 17 months. Complete tumoral resection confirmed by loss of fluorescence significatively increases the median SSP of 6.7 months to 12.9 months (p=0.001559) and the median SG of 12.3 months to 20.9 months (p=0.000559). After 1 year, 81.8% of patients were still alive., Conclusions: Our study confirms the use of fluorescence as an effective method to allow optimal resection of glioblastoma. In addition to neuronavigation, surgical experience, vision and proprioception, fluorescence contributes to achieve a complete tumor resection., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

In the recent years a considerable number of different studies devoted to craniopharyngioma morphology were performed. There are more than 35 factors known up to date that could be related to the craniopharyngioma growth (Ki-67, p53, beta-catenin, p63, Retinoid acid receptors, Galectin-3, MIF, MVD, CK et al.). Despite the such a variety of factors, none of them, except for the Ki-67, strongly correlates with the risk of tumour recurrence and none can be associated with a particular tumour type. Most studies, by the way, focused on a very small number of factors and were performed in relatively small groups of patients. Most publications are devoted to the Ki-67, beta-catenin and p53 studies, and the highest number of patients enrolled to the study was 67. This survey made an attempt to review the literature on the craniopharyngioma biology and to identify further areas of research to obtain data that could affect the choice of treatment and outcome in this complex disease.

A 60-year-old woman was admitted for the treatment of a gastric neuroendocrine tumor (NET) associated with type A chronic atrophic gastritis. The lesion measured 10 mm in diameter, and a computed tomography scan did not reveal any metastatic lesions. Endoscopic submucosal dissection (ESD) was subsequently performed. A histological examination revealed three gastric NETs, two of which exhibited vessel invasion. Endocrine cell micronests associated with a high risk of recurrence were also observed. Therefore, the patient underwent total gastrectomy with lymph node dissection. Because vessel invasion can occur in patients with small gastric NET G1, the use of ESD should be considered to carefully estimate the presence of invasion.

Children and adolescents represent 1-1.5% of all patients with thyroid cancer (TC). The vast majority of TC in children and adolescents is papillary TC; follicular TC (FTC) is exceedingly rare. In this study, we evaluate the clinical and pathological features of FTC in children and adolescents. We also report the risk factors for post-operative tumor recurrence and the associated outcomes. Twenty children and adolescents (under 21 years old) with FTC have been treated and followed at Noguchi Thyroid Clinic and Hospital Foundation since 1946. All patients underwent surgery (lobectomy, 11; subtotal thyroidectomy, 8; and total thyroidectomy, 1), and 8 patients received postoperative external beam radiation therapy. The incidence of FTC in children and adolescents was 1.9% among all FTC patients treated in our hospital. Histopathology revealed vascular and capsular invasion in 9 and 20 patients, respectively. The tumor recurrence rate in FTC with vascular invasion is significantly higher than in those without it (p = 0.038). No other factors were significant. Patients with recurrences were treated with completion thyroidectomy and ¹³¹I radioactive iodine therapy. There were no significant differences in the rates of disease-free survival or cause-specific survival when pediatric/adolescent FTC patients were compared to adults with FTC. FTC is very rare among children and adolescents, but the outcomes are similar to those observed among adults. Vascular invasion is poor prognostic indicator in pediatric/adolescent FTC patients.