Effect of Interstitial Laser Hyperthermia in a Murine Model of Colorectal Liver Metastases: Scanning Electron Microscopic Study

Interstitial laser hyperthermia (ILH) is an in situ ablative technique used to treat colorectal liver metastases. The relatively high recurrence of tumor after treatment by ILH may be related to incomplete destruction. Little is known about the effectiveness of ILH for destroying tumor microvasculature. The aim of this study was to define the changes to the microvascular architecture of tumors after treatment with ILH, specifically focusing on the completeness of tumor vasculature destruction. An intrasplenic induction model of liver metastases in 4- to 6-week-old male inbred CBA mice was used. Laser hyperthermia was applied to liver and tumor tissue using a bare optical quartz fiber from a Medilas Fibertom 4100 Nd:YAG surgical laser generator. The animals underwent microvascular corrosion casting of the livers immediately after application of ILH. Microvascular casts were then prepared and studied by scanning electron microscopy. ILH produced complete, uniform destruction of the tumor microvasculature with compete hemostasis. Blood flow in vessels larger than 100 m diameter had a relatively protective effect, although ILH was able to overcome this barrier effectively by increasing the energy applied. ILH produces complete destruction of tumor microvasculature with hemostasis. The protective effect of blood flow in larger vessels can be overcome by the appropriate use of higher energy levels.     

Topical analgesics and blood pressure during static contraction in humans

PURPOSE: In decerebrate cats, topical application of analgesic balm (AB) can attenuate the pressor response to electrically induced static contraction. We examined the possibility that this phenomenon also occurs in humans and determined whether such effects were limited to a local action on the contracting muscle (e.g., attenuations of the action of groups III and IV muscle afferents that cause the exercise pressor reflex) or whether they also may have affected active muscle blood flow and/or central command. METHODS: Blood pressure (mean arterial pressure (MAP)), heart rate (HR), brachial artery blood flow (BABF), and relative perceived exertion (RPE) were assessed at rest and during 90 s of static handgrip contraction before and 50 min after application of a commercially available AB (1% capsaicin, 12.5% methyl salicylate) to the skin of the forearm muscles. RESULTS: AB attenuated the MAP response to contraction (19 +/- 3 vs 27 +/- 5 mm Hg) but had no effect on the HR response. Absolute BABF was enhanced at rest and during contraction, but absolute (118 +/- 47 vs 114 +/- 47 mL x min) and percent increases (83 +/- 31 vs 55 +/-19%) were not statistically different between conditions. AB appeared to slightly enhance RPE, but this was also the case in a control protocol where only the vehicle (petroleum jelly) was used and no change in the blood pressure response was seen. CONCLUSIONS: AB attenuates contraction-induced increases in MAP that do not seem to be related to alterations in perfusion of active muscle or central command. Effects appear to be localized to the active skeletal muscle and likely involve reductions in sensitivity of groups III and IV muscle afferents to local chemical and/or mechanical stimulation.     

Mechanisms underlying quercetin-induced vasorelaxation in aorta of subchronic diabetic rats: an in vitro study

In this study, the mechanisms involved in vasorelaxant effect of the flavonoid quercetin was investigated in isolated aortic rings from streptozotocin (STZ)-diabetic rats. After 4 weeks, addition of quercetin (0.1 microM-1 mM) caused a significant dose-dependent relaxation of noradrenaline (NA)- and KCl-preconstricted rings in both control and diabetic groups with a significant inter-group difference of P<0.01. Furthermore, both nitro-L-arginine-methyl ester (L-NAME, 100 microM) and indomethacin (10 microM) markedly attenuated the vasorelaxant responses following quercetin application. Meanwhile, endothelium removal significantly attenuated the quercetin-induced vasorelaxation. It is concluded that the quercetin can relax the preconstricted rings of aorta in subchronic STZ-diabetic rats through nitric oxide- and -prostaglandin-mediated pathways, which themselves could be considered as endothelium-dependent.     

Simultaneous integrated boost for breast cancer using IMRT: a radiobiological and treatment planning study

PURPOSE: The purpose of this work is to explore the possibility of using intensity-modulated radiation therapy (IMRT) to deliver the boost dose to the tumor bed simultaneously with the whole-breast IMRT to reduce the radiation treatment time by 1-2 weeks. METHODS AND MATERIALS: The biologically effective dose (BED) for different treatments was calculated using the linear-quadratic (LQ) model with parameters previously derived for breast cancer from clinical data (alpha/beta = 10Gy, alpha = 0.3Gy(-1)). A potential doubling time of 15 days (from in vitro measurements) for breast cancer and a generic alpha/beta ratio of 3 Gy for normal tissues were used. A series of regimens that use IMRT as initial treatment and an IMRT simultaneous integrated boost (SIB) were derived using biologic equivalence to conventional schedules. Possible treatment plans with IMRT SIB to the tumor bed were generated for 2 selected breast patients, 1 with a shallow tumor and 1 with a deep-seated tumor. Plans with a simultaneous integrated electron boost were also generated for comparison. Dosimetric merits of these plans were evaluated based on dose volume histograms. RESULTS: A commonly used conventional treatment of 45 Gy (1.8 Gy x 25) to the whole breast and then a boost of 20 Gy (2 Gy x 10) is biologically equivalent to an alternative plan of 1.8 Gy x 25 to the whole breast with a 2.4 Gy x 25 SIB to the tumor bed. The new regime reduces treatment time from 7 to 5 weeks. For the patient with a deep-seated tumor, the IMRT plans reduce the volume of the breast that receives high doses (compared with the conventional photon boost plan) and provides good coverage of the target volumes. CONCLUSION: It is biologically and dosimetrically feasible to reduce the overall treatment time for breast radiotherapy by using an IMRT simultaneous integrated boost. For selected patient groups, IMRT plans with a new regimen can be equal to or better than conventional plans.     

Magnitude and impact of treatment delays on weeknights and weekends in patients undergoing primary angioplasty for acute myocardial infarction (the cadillac trial)

In 2,082 patients in the CADILLAC trial, the outcomes of patients presenting during peak hours were compared with those presenting during peak hours (Monday to Friday 8a.m. to 8 p.m., n = 1,047, 51%) were compared with those of patients presenting during off-peak hours (weeknights from 8 p.m. to 8 a.m. and weekends, n = 989, 49%). Although treatment times to percutaneous coronary intervention (PCI) were delayed approximately 21 minutes, in patients with acute myocardial infarctions occurring on weeknights and weekends, this modest delay did not adversely affect procedural success, myocardial recovery, or survival after PCI.     

Response of T and B lymphocytes in the spleen, lymph nodes and mammary tumors in rats treated with human soluble tumor-associated antigens and commercial human albumin

We showed previously that soluble tumor-associated antigens (sTAA) isolated from breast cancer patients could suppress chemically-induced tumorigenesis in rats in comparison to the effect of commercial human albumin (CHA). Herein we analyze the possible mechanism of those findings. The following groups of mammary tumor-bearing rats were used in the studies: i) control rats treated with saline; ii) rats treated with CHA; and iii) rats treated with human sTAA. Different zones of the spleen, regional lymph nodes and tumors and their cellular content (B and T cells) were analyzed using the methods of morphometry and immunohistochemistry. Treatment of tumor-bearing rats with CHA resulted in a significant decrease in the size of the germinal center of the follicles. The number of B lymphocytes in the mantle layer of the follicles, the marginal zone and red pulp decreased significantly. The number of CD8+ T cells also decreased in the marginal zone and red pulp, whereas the number of CD4+ T cells increased in the periarterial lymph sheath (PALS) and the red pulp. Reaction of the spleen to vaccination with sTAA manifested in a significant increase in the size of most areas of the white pulp and in the number of B lymphocytes. In lymph nodes from control rats or those treated with CHA, CD8+ lymphocytes mainly accumulated in the paracortical zone. In rats treated with sTAA, CD8+ lymphocytes accumulated also in the medulla. The number of CD4+ T cells in these rats sharply increased and accumulated mainly in the medulla around the vessels. The total number of lymphocytes was changed differently in different areas of tumors (peripheral vs. at depth). The number of CD8+ cells significantly increased at depth of tumors, and also the ratio in the number of these cells at depth of tumors compared to a periphery increased. No difference was found in response of lymph cells to different types of treatment. All findings indicated a strict antitumor effect of vaccination with the sTAA, which prevents the development of insufficiency of the immune system when an intensive immune reaction takes place.     

Breast hamartoma: fine-needle aspiration cytologic finding

BACKGROUND: Breast hamartoma is an unusual, well-circumscribed, tumor-like mass entering into the differential diagnosis of benign breast disease. To the authors' knowledge, the cytology of these lesions has not been well described. Although fine-needle aspiration is a well established procedure for the detection of breast carcinoma, its utility in classifying benign breast disease is less clear. METHODS: Fine-needle aspirates from eight patients with histologically proven hamartomas were reviewed. None of the cases had a preoperative fine-needle aspiration diagnosis of hamartoma. Cytologic characteristics were retrospectively evaluated in a semiquantitative manner and compared with the histologic findings. RESULTS: The aspirates were moderately cellular and contained sheets of both bland ductal cells and lobular units. Adipose tissue was present in varying amounts. Bipolar stromal nuclei were readily apparent, whereas intact stromal fragments were less prominent. Cytologic atypia was uniformly absent. CONCLUSIONS: The cytology of breast hamartomas shows considerable overlap with other benign breast disease and is unlikely to be interpreted as malignant. The findings of intact lobular units and a relative paucity of stroma in an aspirate from a well circumscribed breast lesion may suggest the diagnosis of hamartoma.