Tumor-feeding Vessels Research Articles

Percutaneous Treatment of Hepatocellular Carcinoma in Patients with Transjugular Intrahepatic Portosystemic Shunts

To assess the role of transcatheter arterial chemoembolization (TACE) and percutaneous ethanol injection (PEI) in patients with hepatocellular carcinoma (HCC) and transjugular intrahepatic portosystemic shunts (TIPS). Between January 1999 and September 2004, 6 patients with HCC and TIPS were treated with either TACE (n = 3) or TACE in combination with PEI (n = 3). One patient had a known advanced, untreated HCC prior to TIPS. In the remaining 5 patients HCC was diagnosed 14, 17, 51, 69, and 76 months respectively after elective TIPS. TACE was performed using a mixture of 30-60 mg of epirubicin and 10 ml of lipiodol following superselective catheterization of tumor-feeding vessels. PEI was performed under CT guidance. The mean follow-up time after treatment of HCC was 26.2 months (range 7-46 months). During follow-up, all patients were free of rebleeding. Two patients died 7 and 38 months after one session of TACE and PEI (77 months after TIPS) and three sessions of TACE (91 months after TIPS), respectively. The cause of death was liver failure (Child-Pugh class C) and peritonitis, respectively. A third patient underwent liver transplantation 24 months after TIPS and several sessions of TACE. In the remaining 3 patients, the HCC is well controlled 13, 30, and 46 months after repetitive percutaneous treatment without signs of hepatic deterioration or metastasis. Transcatheter arterial superselective chemoembolization and percutaneous ethanol injection seems to be beneficial even in HCC patients treated with TIPS, provided that the liver function is adequate.

Three-dimensional imaging of skin melanoma in vivo by dual-wavelength photoacoustic microscopy

Dual-wavelength reflection-mode photoacoustic microscopy is used to noninvasively obtain three-dimensional (3-D) images of subcutaneous melanomas and their surrounding vasculature in nude mice in vivo. The absorption coefficients of blood and melanin-pigmented melanomas vary greatly relative to each other at these two optical wavelengths (764 and 584 nm). Using high-resolution and high-contrast photoacoustic imaging in vivo with a near-infrared (764-nm) light source, the 3-D melanin distribution inside the skin is imaged, and the maximum thickness of the melanoma (approximately 0.5 mm) is measured. The vascular system surrounding the melanoma is also imaged with visible light (584 nm) and the tumor-feeding vessels found. This technique can potentially be used for melanoma diagnosis, prognosis, and treatment planning.

Analysis of Tumor Vessel Supply in Lewis Lung Carcinoma in Mice by Fluorescent Microsphere Distribution and Imaging with Micro- and Flat-Panel Computed Tomography

In lung carcinomas the blood supply varies depending on tumor type and stage and can develop from pulmonary or bronchial circulation, or both. To examine this in vivo, primary bronchogenic Lewis lung carcinoma cells were intratracheally instilled in C57BL/6 mice. Within 7 days, histological examinations showed progressive tumor growth at the peripheral parenchymal region. The relative contribution of tumor blood supply via the pulmonary and systemic arteries was studied in detail using fluorescent microspheres (10 microm). When compared to healthy lung parenchyma (13:1), Lewis lung carcinoma tumor tissue (52:1) showed a fourfold increase in pulmonary to systemic microspheres, indicating that the pulmonary arteries are the predominant tumor-feeding vessels. After filling the vessels with a vascular cast, the microanatomy of vessels being derived from the pulmonary artery was visualized with micro computed tomography. Flat-panel volumetric computed tomography provided longitudinal visualization of tissue bridges between the growing tumor and the pulmonary vasculature. In this model of peripheral parenchymal malignancy, new imaging techniques allowed effective visualization of lung tumor growth and vascularization in living mice, demonstrating a pulmonary blood supply for lung tumors.

Induction of tumour blood flow stasis and necrosis: a new function for epinephrine similar to that of combretastatin A-4 derivative AVE8062 (AC7700).

AVE8062, a derivative of combretastatin A-4, has a strong stanching effect on tumour blood flow (TBF), which leads to complete blockage of nutrient supply to solid tumours and their necrosis. Previously, we reported that TBF stasis is due to increased arteriolar resistance caused by AVE8062 and a lasting decrease in perfusion pressure in tumour-feeding vessels. Here, we measured changes in TBF in rat solid tumour LY80 during continuous administration of AVE8062-like epinephrine or four catecholamines that are unlike AVE8062 (norepinephrine, dopamine, methoxamine, and metaraminol) to the region of increased vascular resistance. Venous administration of 0.3 mg ml−1 epinephrine caused TBF to fall immediately to near zero, where it remained throughout the administration period. With a 30-min drug administration, TBF began to recover immediately when drug administration halted. With a 60-min epinephrine administration, TBF recovered somewhat, but not to the previous level. With drug administration of 120 min, TBF did not recover during the subsequent 8 h. Likewise, 0.1 mg ml−1 epinephrine produced irreversible occlusion after 120 min of administration. In contrast, 120 min of administration of the four other catecholamines resulted in no occlusion. Only the group given 0.3 mg ml−1 epinephrine (not that given methoxamine) showed significantly greater necrosis than the control. We conclude that, for epinephrine to cause irreversible occlusion of these vessels, a marked decrease in perfusion pressure in tumour-feeding blood vessels is necessary and should be maintained for 2 h. This conclusion is consistent with the previously demonstrated mechanism of irreversible arteriole occlusion caused by AVE8062. AVE8062 and epinephrine appear to have the same mechanism of action regarding induction of tumour blood flow stasis.

Occlusion of infusion vessels on γ-linolenic acid infusion

γ-linolenic acid (GLA) is known to have selective tumoricidal action. In this study, the effect of lithium salt of GLA conjugated to iodized lymphographic oil (LGIOC) was injected intra-arterially close to the origin of tumor-feeding vessel(s) was studied. Four patients with stage 4 cancer disease (2 with hepatocellular carcinoma, 1 with giant cell tumor of the bone, and one with renal cell carcinoma), were selected for the study. Angiography, radiography and computed axial tomography were performed prior to and immediately after the injection of LGIOC and at periodic intervals. All four patients tolerated the treatment well. The most significant observation was the complete occlusion of the tumor-feeding vessels after LGIOC injection. Follow-up angiograms performed in all the patients showed occlusion of the tumor-feeding vessels is more or less permanent. A significant reduction in the size of the tumor was also observed in these patients. LGIOC showed occlusion of tumor-feeding vessels after infusion, and further studies are needed to confirm these preliminary results.

Subretinal Mass as a Presenting Sign of Posterior Scleritis: A Case Report

We report a case of an unusual clinical presentation of posterior scleritis. A 40-year-old woman suffered from sudden blurred vision in her left eye for 1 day. She had no systemic or autoimmune diseases. Fundus examination revealed a subretinal mass (10.5 x 6 mm in basal diameter) in the nasal-superior quadrant extending from the optic disc to the periphery. Overlying retinal striae were obvious. Optic disc hyperemia and mild edema were noted. Fluorescein angiography did not show dye leakage or tumor-feeding vessels. Ultrasonography showed high internal reflectivity of the subretinal mass and thickened sclera with T-sign. Under the impression of posterior scleritis, corticosteroids and nonsteroidal anti-inflammatory drugs were given orally and topically. After 4 weeks, the subretinal mass disappeared without any sequelae. The patient recovered full vision. This case suggests that posterior scleritis is among the differential diagnoses for a fundus mass. There has been no other similar report in Taiwan.

RETRACTED: Abrupt and complete occlusion of tumor-feeding vessels by γ-linolenic acid

This article has been retracted by the Publisher. Reason: This article was previously published in Nutrition, Volume 18, Issue 7–8, pages 662–664 and inadvertently published again in Nutrition, Volume 18, Issue 9, pages 767–769.

Abrupt and complete occlusion of tumor-feeding vessels by γ-linolenic acid

Abrupt and complete occlusion of tumor-feeding vessels by γ-linolenic acid

Anti-angiogenic treatment strategies for malignant brain tumors.

The use of angiogenesis inhibitors may offer novel strategies in brain tumor therapy. In contrast to traditional cancer treatments that attack tumor cells directly, angiogenesis inhibitors target at the formation of tumor-feeding blood vessels that provide continuous supply of nutrients and oxygen. With respect to brain tumor therapy, inhibitors of angiogenesis display unique features that are unknown to conventional chemotherapeutic agents. The most important features are independence of the blood-brain barrier, cell type specificity, and reduced resistance. Malignant brain tumors, especially malignant gliomas, are among the most vascularized tumors known. Despite multimodal therapeutic approaches, the prognosis remains dismal. Thus, angiogenesis inhibitors may be highly effective drugs against these tumors. In a clinical setting, they could be applied in the treatment of multiple tumors or postsurgically as an adjuvant therapy to prevent recurrence. This article provides an overview of current anti-angiogenic treatment strategies with emphasis on substances already in clinical trials or candidate substances for clinical trials. The cellular and molecular basis of these substances is reviewed.

Perfusion to Colorectal Cancer Liver Metastases Is Not Uniform and Depends on Tumor Location and Feeding Vessel

Future effective therapies for hepatic metastases may depend on a better understanding of perfusion to these tumors. The purpose of this project was to define blood flow to colorectal cancer liver metastases using quantitative autoradiography (QAR). Liver tumors were established in F1hybrids of WF × BN rats by intrasplenic injection of a DMH-induced rat colon adenocarcinoma. Rats underwent laparotomy 4–5 weeks later and [14C]iodoantipyrine (a radiotracer) was infused via the hepatic artery (HA) or portal vein (PV). Livers were harvested, frozen in liquid nitrogen, and sectioned at 20 μm through all tumors. QAR compared optical density of cross sections of tumors to surrounding normal liver tissue. Tumor:liver perfusion ratios (T/L PR) and tumor center:tumor periphery perfusion ratios (C/P PR) were calculated. All groups were analyzed with regard to tumor location and size. Seventy-seven tumors in 6 rats in the HA infusion group were analyzed; 74 tumors in 8 rats in the PV group were analyzed. Statistical analysis was by repeated measures analysis of variance. Mean HA T/L PR = 0.97 ± 0.13, mean PV T/L PR = 0.25 ± 0.11. Mean HA T/L PR for deep tumors was 1.38 ± 0.17 and for superficial tumors was 0.57 ± 0.15 (P< 0.01). Mean HA T/L PR for small tumors was 1.09 ± 0.12 and for large tumors was 0.86 ± 0.21 (P= 0.27). Mean PV T/L PR for deep tumors was 0.27 ± 0.14 and for superficial tumors was 0.24 ± 0.15 (P= 0.71). Mean PV T/L PR for small tumors was 0.31 ± 0.15 and for large tumors was 0.20 ± 0.14 (P= 0.54). Mean HA C/P PR = 1.15 ± 0.15, mean PV C/P PR = 0.81 ± 0.14 (P= 0.06). Mean HA C/P PR for small tumors was 1.37 ± 0.16 and for large tumors was 0.92 ± 0.17 (P= 0.01). Mean PV C/P PR for small tumors was 0.78 ± 0.18 and for large tumors was 0.72 ± 0.13 (P= 0.71). HA perfusion of tumors is significantly higher than PV perfusion compared to surrounding normal liver tissue. HA perfusion varies significantly depending on tumor location.There was a trend toward HA perfusion to the tumor center being slightly greater than to the periphery whereas the reverse was seen for PV perfusion. Tumor size did not affect overall perfusion but it did affect regional HA tumor perfusion.

The role of color duplex ultrasound in diagnosis and differential diagnosis of carotid body tumors

Currently the diagnosis of tumorous lesions of the carotid bifurcation is the domain of magnetic resonance imaging (MRI) and digital subtraction angiography (DSA). So far, colour Doppler imaging (CDI) has not been playing an important part in this field. The aim of this study was to define the diagnostic value of CDI in the evaluation of these tumours related to the big arteries and to compare the different imaging techniques. 6 female patients with suspected tumours of the carotid bifurcation were examined with CDI. Additionally 5 MRI examinations and 3 preoperative diagnostic DSA examinations were performed in the same patients. Pathologically, there were 4 typical carotid body tumours, 1 neuroma of the sympathetic trunk and 1 multifocal paraganglioma of the neck. In carotid body tumours we found a characteristic broadening of the bifurcation with shifting of the internal carotid artery posteriorly and laterally and of the external carotid artery anteriorly and medially. The highly vascularized tumour is surrounded by the arteries. This combination of ultrasound findings was absent in cases of sympathetic neuroma and multifocal paraganglioma. No additional information was achieved with MRI and DSA. CDI and MRI evaluation revealed the same diagnostic value in cases of vascularised tumours of the carotid bifurcation. CDI proved to be as accurate as DSA in the imaging of the big arteries and their relationship to the tumour, as well as of the small tumour feeding vessels. Therefore DSA may be omitted as an invasive diagnostic tool in the diagnosis of carotid body tumours.

Endothelin-1 Expression by Human Hepatocellular Carcinoma

Plasma levels of endothelin-1 (ET-1) are markedly higher in patients with hepatocellular carcinoma (HCC) than in normal controls. In order to further investigate this, we evaluated ET-1 immunoreactivity and mRNA expression in human HCC tissue. 70% (14/20) of the tumor tissues immunostained positively with ET-1 antibody and a significant association was observed between immunostaining in cells lining the tumor feeding vessels and tumor vascularity as determined by hepatic angiography. Moreover, the neoplastic hepatocytes in the tumors also stained positively with ET-1 antibody. All of the HCC tissue samples which immunostained for ET-1 also expressed ET-1 mRNA, indicating that ET-1 is actively synthesized by the tumors.

MR imaging and MR angiography in preoperative evaluation of intracranial meningiomas

A group of 41 patients with intracranial meningiomas were examined by MR imaging (MRI) and MR angiography (MRA) to assess the. clinical value of MRA in the preoperative evaluation of these patients. The results of MRA were compared with the results of intraarterial cerebral catheter X-ray angiography (XRA; n = 19) and with the operative findings (n = 41 ): Our results showed a good correlation between MRA and XRA/surgery in demonstrating the relationship between the tumor and adjacent venous and arterial structures. Use of MRA was also helpful in demonstrating the degree of intrinsic tumor vascularity. It also supplied important information for operative planning Adjunct XRA was mandatory if detailed information about tumor-feeding vessels was requested by the neurosurgeon, especially in highly vascularized angiomatous meningiomas and in meningiomas suspected of tumor feeding by vessels of the internal carotid artery.

Transendothelial migration activity of lymphokine-activated killer (LAK) cells.

With an in vitro static system using HUVEC (human umbilical vein-derived endothelial cells) cultured on type I collagen gel, we investigated the transendothelial migration activities of I1-2 activated killer (LAK) cells. Our results indicate that in comparison with unstimulated T cells, LAK cells exhibit strong transendothelial migration activity, as well as increased adhesiveness to HUVEC. Pretreatment of HUVEC for 24 h with rINF-gamma, rTNF-alpha and rIL-1 beta enhanced the LAK cell migration. The increase in the percentage of migration of LAK cells was greater than that of the percentage of adhesion but significantly less than the increase in the percentage of migration of resting T cells. The results of blocking studies using mAb strongly suggest that the enhanced migration of LAK cell was probably attributed to nonspecifically increased binding to HUVEC and markedly enhanced chemokinetic activity that was dependent primarily on the LFA-1 molecule. Among LAK cells, there were considerable differences in the migration activities of the various phenotypes. CD8+T-LAK migrated preferentially to CD4+T-LAK. CD16+ NK-LAK showed increased adhesion but somewhat decreased migration activities. However, rINF-gamma treatment of HUVEC for 24 h promoted vigorous migration of CD16+ NK-LAK, which suggests that endothelium regulate the migration of LAK cells. Based on these observations, we proposed that LAK cells, if transferred into tumor feeding vessels, can migrate into tumor tissue in considerable numbers and efficiently make contact with individual tumor cells to produce preferable clinical effects.

Magnetic Resonance Imaging of Orbital Lymphangioma with and without Gadolinium Contrast Enhancement

Lymphangioma is a vascular tumor of the orbit with a propensity for recurrent hemorrhage. These tumors may be difficult to diagnose in young patients who present with sudden proptosis due to hemorrhage into a previously unrecognized lesion. Magnetic resonance imaging (MRI) should be ideally suited for evaluating lymphangioma due to the unique ability of MRI to characterize hemorrhage because of the paramagnetic qualities of hemoglobin. The authors performed T1-, T2-, and proton density-weighted MRI on 12 patients with orbital lymphangioma. Six patients underwent MRI with gadolinium-DTPA contrast enhancement. The MRI studies were performed using a 1.5 Tesla super-conducting magnetic resonance unit, except for 3 early studies performed with a 0.5 Tesla unit. All studies were performed with orbital surface coil imaging. Computed tomography (CT) was performed in 10 patients. Tumor was visible on MRI in all 12 patients. Magnetic resonance imaging delineated clearly the internal structure of subacute and chronic hemorrhagic cysts, and differentiated between these tumors because of the different paramagnetic qualities of subacute hemorrhage compared to chronic hemorrhage. In two patients, MRI detected large tumor feeding vessels by the flow void phenomenon unique to MRI. Computed tomography did not detect these vessels. Gadolinium-contrasted T1-weighted MRI did not further delineate or characterize the tumor. Magnetic resonance imaging is the modality of choice for imaging orbital lymphangioma because of its unequalled differentiation of hemorrhagic cysts, and its unique ability to detect tumor feeding vessels by the flow void phenomenon.

Effects of Bradykinin on the Hemodynamics of Tumor and Granulating Normal Tissue Microvasculature

Bradykinin (BK) is an important endogenous mediator of microvascular flow modulation. Since the structure of the microcirculation is very different in tumor tissues than in normal tissues, bradykinin may elicit different responses in tumors. This study was designed to test the hypothesis that local administration of bradykinin increases blood flow preferentially in normal tissue relative to adjacent tumor tissue, resulting in a "vascular steal" phenomenon. Microvessel diameters (D), velocities (Vc), length densities, shear rates, and intermittent flow frequencies were measured every 10 min before, during, and after 40 min exposure to BK in rats with dorsal flap window chambers 9 days after tumor implantation. Separate studies were made of normal vessels outside the tumor margin, the hypervascular tumor periphery, and the tumor center. Bradykinin was administered with a suffusion medium flowing over the tissue at 1-2 ml/min with a BK concentration of 1.6 x 10(7) M. Administration of BK created five distinct changes in normal and tumor vessel function that varied over time, but coincidentally reached a maximum effect after 20 min exposure to BK. In normal vessels, increased Vc and D led to increased flow, which reached a peak 20 min after onset of suffusion with BK. In contrast, in centrally located tumor vessels, decreased D and Vc were observed in most vessels during the initial 10-20 min of suffusion. In addition, there was a significant increase in intermittent flow frequency in tumor central vessels, which peaked after 20 min of suffusion with BK. These five separate observations that coincided at 20 min of suffusion are consistent with a "vascular steal" phenomenon. The increase in normal microvessel D and Vc at 20 min suggests that BK causes vasodilation in arterioles. The coincident decrease in tumor microvessel D and Vc suggests that tumor feeding vessels are less able to respond to BK by vasodilating. The concomitant increase in intermittent flow frequency in tumor vessels suggests that a reduction in pressure drop occurred after 20 min exposure to BK, which is also consistent with "vascular steal." Since BK is also known to increase vascular permeability, it is possible that increases in interstitial fluid pressure brought on by exposure to BK contributed to the observed reduction in tumor blood flow. In normal vessels, reduced D and Vc, relative to peak values, were noted after 40 min suffusion with BK. Adherence of leukocytes to the vessel walls was prominent and microthrombi were also observed during this period. No evidence of such adhesion was seen in tumor vessels, although microthrombi were observed.(ABSTRACT TRUNCATED AT 400 WORDS)

Glomus tumors of the temporal bone--surgical concept and results

Between 1985 and 1991, 36 patients with glomus tumors of the temporal bone were operated. More than 60% of the patients presented with an advanced disease (Class C and D) according to the initially discret and slowly progressive clinical signs. Pulsatile tinnitus, hearing loss and paresis of the lower cranial nerves IV to XII were most often found. The management of the patients requires a complete surgical resection with different approaches depending on the extension of the tumor. High resolution CT of the temporal bone and selective angiography of the tumor feeding vessels proved as reliable and necessary imaging tools to determine the size of the tumor and thereby the surgical procedure. Class A tumors (n = 4) were completely resected by an enaural transmeatal approach. Class B tumors (n = 10) were removed completely in all cases by a combined transmeatal-transmastoid approach. A conductive hearing loss in 2 cases and transient facial paresis in one case were observed. Class C tumors (Glomus jugulare tumors, n = 16) required an infratemporal fossa approach type A. A complete resection was achieved in 87.5%. Class D tumors (n = 6) with intracranial extension were managed in a two stage otoneurosurgical procedure. Due to the tumor size and the required surgical procedure a higher incidence of functional lesions (combined hearing loss, vertigo, cranial nerve pareses) was observed. A facial paresis occurred in all cases but was transient in most of them. The results show that functional conservation surgery for glomus tumors of the temporal bone is only possible in Class A and B and some of the Class C tumors. This requires an early diagnosis.

Nodular hepatocellular carcinoma: treatment with intraarterial injection of I-131 Lipiodol

Twenty four patients with hepatocellular carcinoma who refused surgery or had unresectable tumor ranging 2.5 to 8.0 cm in size were treated with intrahepatic arterial injection of iodine-131-labeled iodized oil (I-131 Lipodol) in an attempt to achieve internal radiation of tumor. 555-2,220 MBq in 3-8 ml of I-131 Lipiodol was injected into the hepatic artery or proximal to the tumor feeding vessel depending on the tumor size. Tumor size reduction was observed in 88.9% of tumor smaller than 4.0 cm in diameter, 65.5% between 4.1 to 6.0 cm, and 25.0% of larger than 6.1cm, respectively. The tumor size reduction was corresponded to the gradual drop of serum AFP levels, decreased uptake on gallium-67 scintigraphy, and devascularization on follow-up angiography. Tumors having significant A-V shunts revealed further tumor growth. Adverse reactions from the treatment include fever, mild abdominal pain, nausea and elevation of transaminases. These have been mild and well-tolerated by the patients. This method was able to provide long term local control without complications related to thyroid, lung, GI tract and bone marrow.

A CASE OF RETROPERITONEAL MALIGNANT FIBROUS HISTOCYTOMA

Malignant fibrous histiocytoma (MFH) of the retroperitoneum is rare in Japan. We have experienced one case of this disease. We present this case with a review and discussion of the literature. Case report 28-year-old woman presented with right hypochondralgia. She underwent cholecystectomy with the diagnosis of cholecystitis. The operative finding was a tumor, 10 cm in diameter, adjacent to the upper pole of the right kidney. She was referred to our hospital on Oct. 8, 1984, with a palpable tumor below the right subcostal margin. Laboratory data showed minimal changes. By angiography, A. capusularis of inf. adrenal artery were demonstrated to be the tumor's feeding vessels. On Nov. 6, 1984, she underwent tumor resection including the regional lymph-node. The pathological finding was MFH, of the retroperitoneum, without lymph-node metastasis. She was given postoperative chemotherapy, and was tumor-free 12 months after the operation. There have been 23 cases reported of MFH, of the retroperitoneum in Japan past 10 years. Among them, all 13 cases of urinary tract examination showed a variety of abnormalities. Computerized tomography demonstrated liver metastasis in one of 10 patients. Ultrasound sonography in two cases was also useful to detect the tumor's architecture. Angiography, performed in 13 cases, was the most important diagnostic tool in order to identify the origin of the tumor and assess resectability. Among 18 operative cases, 11 were combined with radiation and/or chemotherapy.

Computed tomographic diagnosis and differential diagnosis of juvenile angiofibroma and angiomatous polyps

Juvenile angiofibromas (JAF) and angiomatous polyps (AP) are vascular histologically benign tumors presenting with an identical clinical triad. Both lesions can be differentiated by their typical geographic pattern of growth, different pattern of tumor extension and their highly characteristic angiographic and angiocomputertomographic appearance. Time-density curves were of no use in differentiating the big variety of hypervascular lesions from each other. CT images of the vascular tumor phase after bolus injection of contrast medium however showed interesting pathomorphological details, which were extremely useful in differentiating JAF from AP and other vascular tumors. It is our opinion, that invasive angiography for diagnosing JAF has been surpassed, but is further essential for mapping of tumor perfusion, feeding vessels and praeoperative embolization therapy.