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PubMed2002

Clinical assessment of conjunctival and episcleral vessel tortuosity in juvenile dermatomyositis.

PURPOSE: Conjunctival and episcleral vessel tortuosity are thought to be associated features of juvenile dermatomyositis. This study was conducted to determine the interobserver reliability of assessing normal and abnormal conjunctival and episcleral vessels from photographs of patients with and without juvenile dermatomyositis. METHODS: Color and red-free external ocular photographs of each eye of 28 children were assessed by 5 pediatric ophthalmologists from The Hospital for Sick Children. Fifteen of these pairs of photographs were of normal control eyes and 13 were from eyes of patients with juvenile dermatomyositis. On a standardized form each ophthalmologist was asked to determine whether both the conjunctival and episcleral vessels appeared normal or abnormal. Interobserver agreement was calculated by the weighted kappa statistic. The sensitivity and specificity of abnormal vessels for diagnosing juvenile dermatomyositis were also determined. RESULTS: Interobserver agreement for assessing conjunctival and episcleral vessels was 0.18 and -0.005, respectively. The average sensitivity and specificity of the evaluators for correctly assessing conjunctival vessels were 0.70 and 0.70, and for episcleral vessels, 0.67 and 0.47, respectively. CONCLUSIONS: There was low interobserver agreement in distinguishing between normal and abnormal eyes based on conjunctival and episcleral vessels. The sensitivity and specificity for identifying patients with juvenile dermatomyositis based on the appearance of vessels alone were relatively low. The appearance of conjunctival and episcleral vessels should be assessed in the context of other ocular and periocular findings of patients with juvenile dermatomyositis.

Adolescent↗

PubMedDate not supplied

Hybrid finite element-finite difference method for thermal analysis of blood vessels.

A hybrid finite-difference/finite-element technique for the thermal analysis of blood vessels embedded in perfused tissue has been developed and evaluated. This method provides efficient and accurate solutions to the conjugated heat transfer problem of convection by blood coupled to conduction in the tissue. The technique uses a previously developed 3D automatic meshing method for creating a finite element mesh in the tissue surrounding the vessels, coupled iteratively with a 1-D marching finite difference method for the interior of the vessels. This hybrid technique retains the flexibility and ease of automated finite-element meshing techniques for modelling the complex geometry of blood vessels and irregularly shaped tissues, and speeds the solution time by using a simple finite-difference method to calculate the bulk mean temperatures within all blood vessels. The use of the 1D finite-difference technique in the blood vessels also eliminates the large computer memory requirements needed to accurately solve large vessel network problems when fine FE meshes are used in the interior of vessels. The accuracy of the hybrid technique has been verified against previously verified numerical solutions. In summary, the hybrid technique combines the accuracy and flexibility found in automated finite-element techniques, with the speed and reduction of computational memory requirements associated with the 1D finite-difference technique, something which has not been done before. This method, thus, has the potential to provide accurate, flexible and relatively fast solutions for the thermal analysis of coupled perfusion/blood vessel problems, and large vessel network problems.

Biomedical Engineering↗

PubMed1991

Distribution of vascular permeability factor (vascular endothelial growth factor) in tumors: concentration in tumor blood vessels.

Vascular permeability factor (VPF) is a highly conserved 34-42-kD protein secreted by many tumor cells. Among the most potent vascular permeability-enhancing factors known, VPF is also a selective vascular endothelial cell mitogen, and therefore has been called vascular endothelial cell growth factor (VEGF). Our goal was to define the cellular sites of VPF (VEGF) synthesis and accumulation in tumors in vivo. Immunohistochemical studies were performed on solid and ascites guinea pig line 1 and line 10 bile duct carcinomas using antibodies directed against peptides synthesized to represent the NH2-terminal and internal sequences of VPF. These antibodies stained tumor cells and, uniformly and most intensely, the endothelium of immediately adjacent blood vessels, both preexisting and those newly induced by tumor angiogenesis. A similar pattern of VPF staining was observed in autochthonous human lymphoma. In situ hybridization demonstrated VPF mRNA in nearly all line 10 tumor cells but not in tumor blood vessels, indicating that immunohistochemical labeling of tumor vessels with antibodies to VPF peptides reflects uptake of VPF, not endogenous synthesis. VPF protein staining was evident in adjacent preexisting venules and small veins as early as 5 h after tumor transplant and plateaued at maximally intense levels in newly induced tumor vessels by approximately 5 d. VPF-stained vessels were also hyperpermeable to macromolecules as judged by their capacity to accumulate circulating colloidal carbon. In contrast, vessels more than approximately 0.5 mm distant from tumors were not hyperpermeable and did not exhibit immunohistochemical staining for VPF. Vessel staining disappeared within 24-48 h of tumor rejection. These studies indicate that VPF is synthesized by tumor cells in vivo and accumulates in nearby blood vessels, its target of action. Because leaky tumor vessels initiate a cascade of events, which include plasma extravasation and which lead ultimately to angiogenesis and tumor stroma formation, VPF may have a pivotal role in promoting tumor growth. Also, VPF immunostaining provides a new marker for tumor blood vessels that may be exploitable for tumor imaging or therapy.

Amino Acid Sequence↗

PubMed2002

Adenoviral VEGF-C overexpression induces blood vessel enlargement, tortuosity, and leakiness but no sprouting angiogenesis in the skin or mucous membranes.

Vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs) are important regulators of blood and lymphatic vessel growth and vascular permeability. The VEGF-C/VEGFR-3 signaling pathway is crucial for lymphangiogenesis, and heterozygous inactivating missense mutations of the VEGFR-3 gene are associated with hereditary lymphedema. However, VEGF-C can have potent effects on blood vessels because its receptor VEGFR-3 is expressed in certain blood vessels and because the fully processed form of VEGF-C also binds to the VEGFR-2 of blood vessels. To characterize the in vivo effects of VEGF-C on blood and lymphatic vessels, we have overexpressed VEGF-C via adenovirus- and adeno-associated virus-mediated transfection in the skin and respiratory tract of athymic nude mice. This resulted in dose-dependent enlargement and tortuosity of veins, which, along with the collecting lymphatic vessels were found to express VEGFR-2. Expression of angiopoietin 1 blocked the increased leakiness of the blood vessels induced by VEGF-C whereas vessel enlargement and lymphangiogenesis were not affected. However, angiogenic sprouting of new blood vessels was not observed in response to AdVEGF-C or AAV-VEGF-C. These results show that virally produced VEGF-C induces blood vessel changes, including vascular leak, but its angiogenic potency is much reduced compared with VEGF in normal skin.

Adenoviridae↗

PubMed1996

Expression of integrin alpha v beta 3 in small blood vessels of glioblastoma tumors.

Angiogenesis, which promotes tumor proliferation and invasiveness, is mediated by integrin-dependent cell adhesion mechanisms and requires expression of integrin alpha v beta 3. To determine whether integrin alpha v beta 3 is expressed in the small blood vessel hyperplasia characteristic of glioblastoma tumors, we explored the mRNA and protein expression of integrin alpha v, beta 3, beta 5, and beta 1 subunits in small blood vessels in gliomas of various grades and nontumorous brain biopsies. Antisense beta 3 and beta 5 riboprobes hybridized to small blood vessels (endothelial and adjacent mesenchymal cells) in 11 of 11 glioblastomas and 2 of 4 anaplastic astrocytomas, but failed to hybridize to small blood vessels in 12 non-neoplastic specimens and 4 low-grade astrocytomas. In contrast, antisense alpha v and beta 1 riboprobes hybridized to small blood vessels in all of the biopsies. The expression of integrin alpha v beta 3 protein in these vessels was determined by immunohistochemical analysis using anti-integrin subunit-specific antibodies. The findings were similar to those obtained using in situ hybridization: beta 3 subunit protein was detected on small blood vessels in 9 of 12 glioblastoma and 2 of 4 anaplastic astrocytomas, whereas it was not detected in small blood vessels of 10 non-neoplastic brains and 4 low-grade astrocytomas. In contrast, the alpha v and beta 1 subunit proteins were detected in small blood vessels in all of the brain biopsies, whereas the beta 5 subunit protein could not be detected. These data suggest that integrin alpha v beta 3 is expressed in small blood vessels of glioblastoma tumors.

Adult↗

PubMed1998

Progression of cerebral amyloid angiopathy: accumulation of amyloid-beta40 in affected vessels.

Cerebrovascular deposits of amyloid (cerebral amyloid angiopathy, or CAA) are generally asymptomatic, but in advanced cases, they can lead to vessel rupture and hemorrhage. The process of progression in CAA was studied by comparison of postmortem brains with asymptomatic ("mild") CAA to brains with the form of the disease associated with hemorrhage ("severe CAA"). Cortical and meningeal vessels were immunostained for beta-amyloid and examined by confocal microscopy and by systematic quantitative sampling. We focused on 2 quantitative parameters: the proportion of vessels affected by amyloid (a measure of amyloid seeding of vessels) and the amount of amyloid per affected vessel (a measure of growth of existing lesions). Surprisingly, there was no difference between the proportion of affected cortical vessels in mild and severe CAA (0.29 vs 0.32, p = 0.65), but rather an increase in the area of the 40 amino acid form of beta-amyloid per affected cortical vessel (198.5 +/- 38.7 vs 455.8 +/- 100.9 microm2/vessel, p < 0.007). Increasing doses (from 0 to 1 to 2 copies) of the apolipoprotein E epsilon4 allele were also associated with greater amyloid per vessel without change in the proportion of affected vessels within each class of CAA severity. These findings suggest that progression from asymptomatic to advanced CAA reflects progressive accumulation of amyloid in vessels previously seeded with amyloid, and that this process is selectively enhanced by apolipoprotein E epsilon4.

Aging↗

PubMed1998

A fuzzy vessel tracking algorithm for retinal images based on fuzzy clustering.

In this paper we present a new unsupervised fuzzy algorithm for vessel tracking that is applied to the detection of the ocular fundus vessels. The proposed method overcomes the problems of initialization and vessel profile modeling that are encountered in the literature and automatically tracks fundus vessels using linguistic descriptions like "vessel" and "nonvessel." The main tool for determining vessel and nonvessel regions along a vessel profile is the fuzzy C-means clustering algorithm that is fed with properly preprocessed data. Additional procedures for checking the validity of the detected vessels and handling junctions and forks are also presented. The application of the proposed algorithm to fundus images and simulated vessels resulted in very good overall performance and consistent estimation of vessel parameters.

Algorithms↗

PubMed2004

Influence of large intrahepatic blood vessels on the gross and histological characteristics of lesions produced by radiofrequency ablation in a pig liver model.

AIMS: To determine whether the presence of large intrahepatic blood vessels (>/=3 mm) affect radiofrequency (RF)-induced coagulation necrosis, the gross and histological characteristics of RF-ablated areas proximal to or around vessels were examined in normal pig livers. METHODS: An RF ablation treatment using a two-stepwise extension technique produced 12 lesions: six contained vessels (Group A), and the other six were localized around vessels (Group B). RESULTS: Gross examination revealed that the longest and shortest diameters of the ablated lesions were significantly larger in Group B than in Group A. In Group A, patent vessels contiguous to the lesion were present in a tongue-shaped area, whereas the lesions in Group B were spherical. Staining with nicotinamide adenine dinucleotide diaphorase was negative within the ablated area; but, if vessels were present in the ablated area, the cells around the vessels in an opposite direction to the ablation were stained blue. CONCLUSIONS: Roll-off can be achieved with 100% cellular destruction within a lesion that does not contain large vessels. The ablated area was decreased in lesions that contained large vessels, suggesting that the presence of large vessels in the ablated area further increases the cooling effect and may require repeated RF ablation treatment to achieve complete coagulation necrosis.

Animals↗

PubMed1995

Angioscotomata and morphological features of related vessels in automated perimetry.

AIMS: To determine principles which regulate the occurrence of angioscotomata in automated static perimetry, variations in light sensitivity were correlated with the location and diameter of neighbouring retinal vessels. METHODS: Ten normal eyes were tested with the Octopus 2000R, using a 0.431 degree light stimulus. Sensitivity was quantified in points located around the blind spot, according to a regular, 0.5 degree constant, grid pattern. From 336 to 443 locations were tested in each eye. The resulting printouts were superimposed on corresponding fundus photographs. At each tested point, the following five additional variables were evaluated: the diameters of the closest and the second closest vessel (in 0.1 degree units); the distances of the apparent location of the tested point to the closest and the second closest vessel (in 0.25 degree units); and the distance between the two closest vessels (in 0.25 degree units). Altogether, 3869 locations were tested and 23,214 values were quantified. RESULTS: The following two conditions were found to be related to a reduction in sensitivity: (1) proximity (< 0.25 degree) to a large vessel (> or = 0.5 degree in diameter); (2) proximity (< 0.25 degree) to one of two adjacent (< 0.5 degree distant), moderately large vessels (0.3 degree to 0.4 degree in diameter). In condition 1, sensitivity was 51.3% and specificity was 92.2%; in condition 2, sensitivity was 16.2% and specificity was 98.3%; and with a combination of conditions 1 and 2, sensitivity was 67.6% and specificity was 90.5%. Increase by 0.1 degree of an adjacent vessel which was 0.4 degree in diameter markedly affected light sensitivity. CONCLUSION: Modifications in vessel diameter are observed in a number of circumstances, including adaptive vascular response to changes in ambient conditions and obstructive disorders of retinal vessels. These findings indicate that changes in vessel diameter over time can result in fluctuation of sensitivity. It is concluded that, in contrast with what is commonly stated, when ocular media are unaltered and the subject's collaboration is adequate, temporal variations in measured thresholds do not necessarily reflect functional changes in nervous tissues in the visual pathways.

Adult↗

PubMed2004

Variation associated with measurement of retinal vessel diameters at different points in the pulse cycle.

BACKGROUND/AIMS: To assess the variability in retinal vessel measurements at different points in the pulse cycle. METHODS: A healthy white male aged 19 years had 30 digitised images taken at three distinct points in the pulse cycle over a one hour period. A pulse synchronised ear clip trigger device was used to capture images at the desired point in the pulse cycle. Two trained graders measured the retinal vessel diameter of one large arteriole, one large venule, one small arteriole, and one small venule 10 times in each of these 30 images. RESULTS: Within an image, variability was similar between graders, pulse point, and vessel type. Across images taken at the same point in the pulse period, the change from the minimum to maximum measurement was between 6% and 17% for arterioles and between 2% and 11% for venules. In addition, measurements of small vessels had greater changes than large vessels and no point in the pulse period was more variable than another. Ignoring pulse cycle increased variability across images in the large venule, but not in the other vessel types. Mixed effect models were fit for each of the vessel types to determine the greatest source of variability. Controlling for pulse point and grader, the largest source of variability for all four vessels measured was across images, accounting for more than 50% of the total variability. CONCLUSION: Measurements of large retinal venules is generally less variable than measurements of other retinal vessels. After controlling for pulse point and grader, the largest source of variation is across images. Understanding the components of variability in measuring retinal vessels is important as these techniques are applied in epidemiological studies.

Adult↗

PubMed1976

Vessel caliber and branch-angle of human coronary artery branch-points.

Measurements were made of parent and branch vessel diameters and of the included angles of branch-points from postmortem human coronary arteriograms to determine the usefulness of theoretical equations predicting the relationships between parent and branch vessel caliber and between arterial caliber and branch-angle. The formulas were based on the concept that blood vessel size and arrangement provided for blood flow with minimum energy loss. Size relationships between parent vessel and its branches were determined for 42 left main and 53 other epicardial coronary artery branch-points in hearts with angiographically normal arteries. Left main coronary artery branch-points were studied in 68 hearts with various degrees of angiographically defined coronary artery disease. Measured diameters (D) of parent and branch vessels corresponded well to the theoretical formula: (DParent)3 = (DBranch1)3 + (DBranch2)3....,in angiographically normal coronary arteries. The exponent, on the average, is less with increasing grades of vascular disease for left main coronary artery branch-points. Mean area ratio, the sum of the cross-sectional area of the branches divided by the area of parent vessel, decreased with greater arteriographic disease. Area ratio varies with changes in the relative calibers of branch vessels. Fifty-seven branch-angles were determined by graphic analysis of postmortem biplane coronary arteriograms. No relationship could be found between branch-angle and vessel caliber. The included angle between branches varied from 32 degrees to 124 degrees without respect to relative or absolute vessel calibers. The results of these postmortem measurements on human coronary arteriogram suggest that coronary artery caliber may adjust to minimize energy loss at the branch-point but that branch-angle is determined by other factors. Restudy of arteriograms suggests that branch-angle may be determined by branch vessel destination.

Adaptation, Physiological↗

PubMed2004

VE-cadherin is not required for the formation of nascent blood vessels but acts to prevent their disassembly.

We investigated the role of vascular endothelial (VE)-cadherin in blood vessel morphogenesis and established a temporal correlation linking the failure in vessel morphogenesis in VE-cadherin null embryos to a specific step in vasculogenesis. We showed that the sequence in which blood vessels failed followed the order in which they had formed (ie, those forming first--yolk sac, allantoic and endocardial vessels--were the first to display morphologic abnormalities). We next showed that in place of normal reticulated networks of blood vessels, clusters of platelet endothelial cell adhesion molecule-positive (PECAM+) cells formed within cultured allantois explants from VE-cadherin null embryos. Similarly, a function-blocking VE-cadherin antibody, BV13, caused PECAM+ cell clusters to form in cultured allantois explants from normal mice. Finally, we demonstrated that formation of PECAM+ cell clusters in response to BV13 was not due to a disruption in the formation of nascent vessels but was due to the actual disassembly of nascent vessels. Based on these findings, we conclude that the events of de novo blood vessel formation up to the point at which a vascular epithelium forms (ie, nascent vessels with lumens) are not dependent on VE-cadherin and that VE-cadherin, whose expression is up-regulated following vascular epithelialization, is required to prevent the disassembly of nascent blood vessels.

Animals↗

PubMed2006

Orientation of endothelial cell division is regulated by VEGF signaling during blood vessel formation.

New blood vessel formation requires the coordination of endothelial cell division and the morphogenetic movements of vessel expansion, but it is not known how this integration occurs. Here, we show that endothelial cells regulate division orientation during the earliest stages of blood vessel formation, in response to morphogenetic cues. In embryonic stem (ES) cell-derived vessels that do not experience flow, the plane of endothelial cytokinesis was oriented perpendicular to the vessel long axis. We also demonstrated regulated cleavage orientation in vivo, in flow-exposed forming retinal vessels. Daughter nuclei moved away from the cleavage plane after division, suggesting that regulation of endothelial division orientation effectively extends vessel length in these developing vascular beds. A gain-of-function mutation in VEGF signaling increased randomization of endothelial division orientation, and this effect was rescued by a transgene, indicating that regulation of division orientation is a novel mechanism whereby VEGF signaling affects vessel morphogenesis. Thus, our findings show that endothelial cell division and morphogenesis are integrated in developing vessels by flow-independent mechanisms that involve VEGF signaling, and this cross talk is likely to be critical to proper vessel morphogenesis.

Animals↗

PubMed2004

Identification of lymphatic vessels in malignant, adenomatous and normal colonic mucosa using the novel immunostain D2-40.

Distribution of lymphatic vessels in normal and neoplastic colon has been previously analyzed with electron microscopic techniques, as reliable antibodies have not been available for selective lymph vessel staining. A novel monoclonal antibody, D2-40, is recently available to differentiate lymphatic vessels from blood vessels. In this study, we analyzed the distribution of lymphatic vessels in normal colon, adenomas with and without superficial stalk invasion and invasive carcinomas without identifiable polypoid precursor lesions. In contrast to previous studies, we found lymphatic vessels in superficially misplaced stalk stroma in adenomas, and closely associated with early invasive epithelial nests in invasive lesions. Lymphatic vessels were identified within the lamina propria of the in situ aspect of in invasive tumors. We conclude that lymphatic vessel structures are seen more superficially in adenomas and invasive carcinomas than previously described. Since intramucosal carcinomas in adenomas do not metastasize, these lymph vessels may be immature or not communicate with deeper lymphatics. Proliferation and distribution of lymphatic vessels may be related to prognosis and early metastasis.

Adenoma↗

PubMed2001

[Change of NOS activity in hypoxia and cold-induced blood vessels damage and its biological significance].

OBJECTIVES: To explore the therapeutic methods for hypoxia and cold induced blood vessel damage by observing the changes of NO synthase (NOS) activity in hypoxia and development of coldm induced blood vessels damage, and studying the effects of SOD and vitamin C on the changes of NOS activity. METHODS: The main artery was isolated from Wistar rats and exposed to hypoxia and/or cold environment in vitro. LDH activity was measured using an automatic biochemical analyzer and NOS and SOD activities in blood vessels were analyzed respectively by Griess assay and adrenaline autoxidantion method. RESULTS: NOS activity in hypoxia, cold and hypoxia-cold damaged vessels decreased by 18.2%, 19.1% and 25.9% respectively after exposure as compared with the control vessels. The changes of NOS activity were time dependent. The NOS activity in damaged vessels was negatively correlated with LDH activity in the culture medium of the respective vessels. The SOD activity in hypoxia and/or cold damaged vessels also decreased significantly. Giving SOD (200 u/ml) or vitamin C (50 mg/ml) immediately after hypoxia and/or cold exposure increased the NOS activity and SOD activity in the damaged vessels significantly, as compared with the non-treatment controls. CONCLUSIONS: The decrease of NOS activity is closely related to the development of damage induced by hypoxia and/or cold injury. SOD and vitamin C could protect the blood vessels exposed to hypoxia and/or cold from damage, possibly by increasing NOS activity.

Animals↗

PubMed2000

[Clinical research on arteriovenous internal fistula made by various blood vessels].

OBJECTIVE: To compare the permeability and incidence rate of complication of arteriovenous internal fistula made by autogenous, homologous, and artificial Teflon blood vessels. METHODS: Two hundred and forty one cases with arteriovenous internal fistula made by autogenous, homologous, and artificial Teflon blood vessels were followed up to compare the permeability and incidence rate of complication at 6 months, 1 year, 3 years, and 5 years. RESULTS: The incidence rate of complication of autogenous blood vessels was lowest, it had no statistical differences compared with arteriovenous internal fistula made by homologous blood vessels. The permeability of arteriovenous internal fistula made by homologous blood vessels was highest, and it had no statistical differences compared with autogenous blood vessels. The permeability of arteriovenous internal fistula made by artificial Teflon blood vessels was lowest, but the incidence rate of complication was highest, and it had significantly statistical differences compared with arteriovenous internal fistula made by autogenous blood vessels (P < 0.01). CONCLUSION: Arteriovenous internal fistulas made by autogenous and homologous blood vessels have high permeability and low incidence rate of complication, they are superior to the arteriovenous internal fistula made by artificial Teflon blood vessels.

Adolescent↗

PubMed1990

[Improvement in the mechanical properties of artificial blood vessel suitable for the extracranial cerebral artery].

Saphenous vein interposition grafts have been commonly used for the reconstruction of occlusive lesions in the extracranial cerebral vessels, such as carotid or vertebral arteries. In contrast, cerebral revascularization using an artificial blood vessel has not been so common. This is due to the fact that conventional artificial blood vessels have been too firm or too rigid for use in the neurosurgery. Another reason is that the long term patency rate of small caliber artificial blood vessels has usually been inferior to that found in autologous vein grafts. The purpose of this study was to develop a soft and compliant artificial blood vessel suitable for cerebrovascular surgery. This new artificial blood vessel is made of polyurethane, porous in structure (porous polyurethane). Thus, multiple small-sized pores exist both in the inner and outer surfaces, and in the wall of the porous polyurethane graft. To test its mechanical properties, we evaluated stress-strain curves and compliance. In comparison to expanded polytetrafluoroethylene graft (Goretex), which has been one of the most commonly used artificial blood vessels in the cardiovascular surgery, the mechanical properties of the porous polyurethane graft more closely resembled those of the common carotid artery in dogs. Thus, porous polyurethane graft was shown to be a soft and compliant new artificial blood vessel. This means not only that it can be maneuvered with technical ease for anastomosis but also that there is a reduction of compliance-mismatch between the host vessel and the artificial vessel. Compliance mismatch has been documented as a major factor in the inducement of intimal hyperplasia, which causes a delayed occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Blood and lymphatic vessel invasion as prognostic factors for patients with primary resected nonsmall cell carcinoma of the lung with intrapulmonary metastases.

BACKGROUND: The new classification of intrapulmonary metastases of lung cancer was proposed by the American Joint Committee on Cancer; however, the prognostic factors are heterogeneous and not yet fully clarified. In this study, the authors evaluated the prognostic factors for and the possible routes of intrapulmonary metastases. METHODS: The factors influencing the prognosis of primary resected nonsmall cell lung carcinomas with intrapulmonary metastasis in the resected specimens were evaluated according to the Cox proportional hazards model using a total of 66 nonsmall cell lung carcinomas. The possible routes of tumor spread via the blood or lymphatic vessels also were evaluated. RESULTS: The overall 5-year survival rate was 26.1%, and the statistical analysis of survival curves revealed a significant difference with regard to N classification (P = 0.042), site of intrapulmonary metastasis (P = 0.012), blood vessel invasion (P = 0.0046), and lymphatic vessel invasion (P = 0.0267); there were no significant differences in relation to age, sex, histology, differentiation, T classification, tumor size, stage, number of intrapulmonary metastases, or size of intrapulmonary metastasis. Multivariate analysis according to the Cox proportional hazards model identified a significant correlation between survival and blood vessel invasion (P = 0.044) and lymphatic vessel invasion (P = 0.042), suggesting independent prognostic significance. The correlation between site of intrapulmonary metastasis and the ratio of blood or lymphatic vessel invasion showed a significantly lower ratio of blood vessel invasion in cases with intrapulmonary metastases at sites central to the primary lesion or in different segment(s) compared with those in cases with intrapulmonary metastases at sites peripheral to the primary lesion or in ipsilateral different lobe(s), suggesting a possible lymphatic vessel route of tumor spread. CONCLUSION: Blood vessel and lymphatic vessel invasion are important clinical factors in evaluating prognosis and the route of tumor spread in primary resected nonsmall cell carcinoma with intrapulmonary metastasis.

Adult↗