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Photodynamic therapy is a recently introduced treatment for surface malignancies. Since January 1987, 10 patients with endobronchial neoplasms have had bronchoscopic photodynamic therapy at similar dose rates (400 mW/cm) for total atelectasis (2), carinal narrowing with respiratory insufficiency (2), or partial obstruction without collapse (4). Two patients underwent photodynamic therapy as a preliminary to immunotherapy. Histologies included endobronchial metastases (colon, ovary, melanoma, and sarcoma, 1 each; and renal cell, 3) and primary lung cancer (3). The 2 patients with total atelectasis had complete reexpansion after photodynamic therapy, which permitted eventual sleeve lobectomy in 1. Carinal narrowing was ameliorated in the 2 patients seen with inspiratory stridor, thereby permitting hospital discharge. Endoscopically resected fragments after photodynamic therapy exhibited avascular necrosis. These data support further controlled studies of photodynamic therapy by thoracic surgical oncologists to define its limitations as well as to improve and expand its efficacy as a palliative or surgical adjuvant.
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PMID:Bronchoscopic phototherapy at comparable dose rates: early results. 252 11

Osteoradionecrosis (ORN) is not exceptional, despite advances in irradiation techniques. Six cases are reported, involving the pelvis, coxofemoral joint, mandible and vertebrae; in this last case, the semiologic value of the lucent intrasomatic image seen on plain films and tomographies of the vertebrae is underscored. The irradiation dose (above 3 000 rad) is the chief factor in osteoradionecrosis, which may be precipitated by adjuvant factors and potentiating events such as trauma and infection. Pathologic study shows several lesions whose association is suggestive: cell lesions, osteoporosis, vascular lesions, and foci of necrosis. The pathogenic significance of lesions of bone cells is demonstrated, while the part played by vascular lesions is controversial. Involvement of the pelvis and hips following irradiation of pelvic carcinoma is the most common. The scapular girdle and ribs may be involved in irradiation for breast cancer. In involvement of the mandible, remarkable features are its frequency following irradiation of carcinoma of the mouth, the significant part played by potentiating factors, i.e. infection and trauma, severity of complications, i.e. fistulae and hemorrhage, and lastly difficulties of management. Among infrequent sites, involvement of the vertebrae is of interest as it may mimic collapse due to osteoporosis or metastasis. Diagnosis rests on an association of criteria, and fortunately bone biopsy is usually unnecessary. The clinical features, topographical characteristics and course of the disease allow differentiation from bone metastasis; it may be more difficult to distinguish postirradiation sarcoma, which is exceptional, or a number of benign conditions, such as aseptic necrosis, infectious osteoarthritis, and destructive coxarthrosis.
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PMID:[Osteoradionecrosis in adults]. 632 22

Mouse mammary sarcoma cells, line EMT6/Ro, were exposed for 1 min to 1 MHz continuous wave ultrasound over a range of intensities from 0.5 to 30 W/cm2 (spatial peak). The presence of thymine base damage (TBD) products of the 5,6-dihydroxydihydrothymine type was determined by an alkali degradation assay. Production of damage was found to be greatest (approximately 2.7 X 10(-3%) t'/T) at an intensity of 10 W/cm2 and fell off rapidly above and below this intensity. The amount of base damage produced at 10 W/cm2 ultrasound was approximately equivalent to the damage produced by a gamma-ray absorbed dose of 12 krad. Assay of cells immediately after sonication at 10 W/cm2 showed that approximately 14% of the cells had been lysed. Tests showed that it was the DNA of the intact cells, however, which sustained all of the TBD. Survival data demonstrated that of the remaining unlysed cell population approximately 5% were viable, whereas cells exposed to 12 krad showed no survival. Additionally, cells were exposed for up to 5 min at 5 W/cm2. An increase in TBD was demonstrated with increasing time of exposure such that the rate of production at 5 min was approximately three times greater than that of a 1-min exposure. TBD was found to be completely suppressed when cells were sonicated at 10 W/cm2 for 2 min under 4 bar of hydrostatic pressure. Addition of the radical scavengers beta-MEA and cystamine eliminated TBD but had minimal effect on survival. The pressure and scavenger experiments demonstrate that TBD results from cavitation-induced free radicals. Based on the values for both the half-life and diffusion distance of such radicals, our results indicate that at least part of the bubble collapse occurs intracellularly.
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PMID:Production of thymine base damage in ultrasound-exposed EMT6 mouse mammary sarcoma cells. 669 45

During anesthetic preparation of a patient who had received routine radiation therapy for sarcoma of the leg, cardiac collapse occurred following succinylcholine (SCh) administration. Experiments were designed to test the hypothesis that radiation injury to muscle might cause increased sensitivity to SCh similar to that reported in patients with muscle trauma, severe burns, and lesions causing muscle denervation. Venous plasma potassium levels and arterial blood gas tensions were measured in rats after they were given SCh (3 mg/kg) at various times following 60Co irradiation of the hind legs. Nonirradiated rats responded to SCh with a slight but statistically significant increase in plasma K+. Rats subjected to high levels of radiation (10,000 to 20,000 R) and given SCh 4 to 7 days later responded in the same way as the control rats. Plasma K+ levels in rats exposed to a fractionated irradiated dosage (2500 R given twice with a 1-week interval) followed by SCh 1 week later were similar to those in the control group, but when SCh was given 2 weeks later (3 weeks after initial irradiation) there was a marked elevation of plasma K+, from 3.6 to 7.7 meq/L, a statistically significant increase.
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PMID:Succinylcholine-induced hyperkalemia in the rat following radiation injury to muscle. 719 82

The intermediate functional results were assessed for fifty-seven patients who had had a limb-salvage procedure for treatment of a tumor of the shoulder girdle region at our institution from 1980 through 1990. Fifty-three patients had a malignant bone tumor (a sarcoma) and four had an extensive giant-cell tumor. The resections were classified according to the system of the Musculoskeletal Tumor Society. A variety of reconstructive procedures were performed after resection of the tumor, with the choice of procedure depending on the type of resection and the needs of the patient. The functional results were described and graded quantitatively according to the functional rating system of the Musculoskeletal Tumor Society. The average duration of follow-up was 5.3 years (median, 4.6 years) for the forty-seven patients who were still alive at the time of the latest follow-up examination. Eight patients died of disease and two others died of unrelated malignant tumors an average of 1.8 years postoperatively. The resection of the tumor was classified as wide in forty of the fifty-three patients who had a sarcoma and as marginal in thirteen; four patients had local recurrence (two, after a wide resection, and two, after a marginal resection). One of the four patients who had a giant-cell tumor had local recurrence. The functional results were related to the type of resection and the method of skeletal reconstruction. After resection of the entire scapula and the proximal aspect of the humerus, reconstruction with a spacer frequently resulted in asymptomatic superior subluxation of the implant and poor function of the shoulder. After extra-articular resection of the glenoid cavity and the proximal aspect of the humerus with loss of the abductor mechanism, osseous arthrodesis resulted in good function that was superior to that found after reconstruction with a spacer or a proximal humeral replacement prosthesis. Our preferred method to achieve fusion was insertion of an intercalary allograft and a vascularized fibular graft. However, the allograft fractured in three of four patients in whom primary fusion had been obtained with this technique. An osteoarticular allograft inserted after intra-articular resection of the proximal aspect of the humerus and preservation of the abductor mechanism provided good function that was superior to that found after reconstruction with a proximal humeral replacement prosthesis, which produced symptomatic instability that led to a secondary arthrodesis in some patients. However, subchondral fracture and collapse of the osteoarticular allograft occurred in four of eight patients by the time of the latest follow-up examination. The results of all methods of reconstruction were satisfactory with regard to pain, emotional acceptance, and manual dexterity. We believe that the use of a method of reconstruction that is appropriate with regard to the needs of the patient and preoperative counseling regarding the expected functional level and restrictions of activity are critical for a high level of postoperative satisfaction.
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PMID:Limb salvage for neoplasms of the shoulder girdle. Intermediate reconstructive and functional results. 898 65

Apoptosis is a physiological process wherein the cell initiates a sequence of events culminating in the fragmentation of its DNA, nuclear collapse, and finally disintegration of the cell into small, membrane-bound apoptotic bodies. Expression of Fas (APO-1, CD95) Receptor (FasR) and programmed or active cell (PCD) death was studied in childhood astrocytomas (ASTRs) with varying stages of malignancy, including pilocytic ASTR, low grade ASTR, anaplastic ASTR, and glioblastoma multiforme (GBM). The great majority of childhood glial tumors, particularly ASTRs express FasR whereas normal cells in the central nervous system (CNS) do not. FasR represents a transmembrane glycoprotein which belongs to the nerve growth factor/tumor necrosis factor (NGF/TNF) receptor superfamily. Apoptosis within ASTRs is triggered by the binding of FasR to its natural ligand (FasL) or by cross-linking with antibodies developed against FasR. Presence of FasL was also detected in childhood glial tumors. The expression of both FasR and FasL was also observed within the same ASTRs. Therefore, spontaneous, IP regulatory, intratumoral apoptotic cell death (autocrine suicide) is possible in childhood glial tumors. During a systematic, immunocytochemical screening of 42 childhood ASTRs tissues divided according to WHO classification: 6 WHO grade I or pilocytic ASTRs; 14 WHO grade II or low grade ASTRs; 16 WHO grade III or anaplastic ASTRs and 6 WHO grade IV or glioblastoma multiforme (GBM), we detected strong expression (intensity of staining: "A"--the highest possible; number of stained cells: +2 to +4, between 20% to 90%) of FasR, employing 4 microns thick, formalin fixed, paraffin-wax embedded tissue slides. FasR was present on 70% to 90% of tumor cells in pilocytic ASTRs, in 50% to 60% of the tumor cells in low grade ASTRs, in between 30% and 40% of the tumor cells in anaplastic ASTRs, and in between 20% to 35% of GBM cells. The panel of normal tissues employed as positive and negative tissue controls demonstrated presence of FasR in the prenatal thymus, mature tonsils and colonic epithelium. The use of a sensitive, indirect, six step immunoperoxidase or alkaline phosphatase conjugated streptavidin-biotin antigen detection technique provided excellent immunocytochemical results. A broad spectrum of neoplastic cells have been identified to express FasR: 1) carcinomas of epithelial origin, such as breast (ductal invasive, lobular invasive, mucinous), renal cell, gastric, colorectal, endometrial, prostate, pancreas, hepatocellular and large cell and squamous cell lung carcinomas: 2) non-epithelial neoplasms such as B cell mediastinal B cell and nodal non-Hodgkin's lymphomas large granular lymphocytic leukemia of T or NK cell origin malignant fibrous histiocytoma, malignant mesothelioma, leiomyosarcoma, epitheloid sarcoma and alveolar soft part sarcoma, as well as melanomas. Flow cytometry studies have also detected FasR expression on cells of adult T cell, and hairy cell leukemias, as well as in chronic B cell lymphocytic leukemia (BCLL). The coexpression of both FasR and FasL on several malignant cell types may represent an effective mechanism of tumor escape from the cellular immunological response of the host. It has been well established that brain tumors and melanomas produce their autocrine FasL, and even become capable of switching the signal transduction associated with FasL-FasR coupling from the PCD pathway to a tumor growth, proliferative pathway. It seems that the therapeutical use of FasR-FasL (main apoptotic pathway) may represent a new and exciting type of immunotherapy in the treatment of primary childhood glial tumors.
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PMID:Fas (Apo-1, CD95) receptor expression in childhood astrocytomas. Is it a marker of the major apoptotic pathway or a signaling receptor for immune escape of neoplastic cells? 1058 78

Angiogenesis is a characteristic feature of many aggressive tumours and other disorders. Antibodies capable of binding to new blood vessels, but not to mature vessels, could be used as selective targeting agents for immunoscintigraphic and radioimmunotherapeutic applications. Here we show that scFv(L19), a recombinant human antibody fragment with sub-nanomolar affinity for the ED-B domain of fibronectin, a marker of angiogenesis, can be stably labelled with iodine-125 and astatine-211 with full retention of immunoreactivity, using a trimethyl-stannyl benzoate bifunctional derivative. Biodistribution studies in mice bearing two different types of tumour grafted subcutaneously, followed by ex vivo micro-autoradiographic analysis, revealed that scFv(L19) rapidly localises around tumour blood vessels, but not around normal vessels. Four hours after intravenous injection of the stably radioiodinated scFv(L19), tumour to blood ratios were 6:1 in mice bearing the F9 murine teratocarcinoma and 9:1 in mice bearing an FE8 rat sarcoma. As expected, all other organs (including kidney) contained significantly less radioactivity than the tumour. Since the ED-B domain of fibronectin has an identical sequence in mouse and man, scFv(L19) is a pan-species antibody and the results presented here suggest clinical utility of radiolabelled scFv(L19) for the scintigraphic detection of angiogenesis in vivo. Furthermore, it should now be possible to investigate scFv(L19) for the selective delivery of 211At to the tumour neovasculature, causing the selective death of tumour endothelial cells and tumour collapse.
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PMID:Selective targeting of tumour neovasculature by a radiohalogenated human antibody fragment specific for the ED-B domain of fibronectin. 1135 6

Primary tumors of the cardiac valves are rare. One of the most common reasons that left-sided cardiac tumors come to clinical attention is embolization to the systemic circulation. We present two children who suffered left coronary arterial occlusion due to embolization of a sarcoma of the mitral valve. A 6-year-old female who had been admitted to the hospital after cerebrovascular embolization of a fragment of sarcoma of the mitral valve experienced sudden cardiovascular collapse due to occlusion of the left coronary artery. She was placed on extracorporeal membrane oxygenation, and underwent coronary embolectomy and resection of the tumor from the mitral valve and its tendinous cords. Left ventricular function did not improve, and she underwent orthotopic heart transplantation. On follow-up 32 months after transplant, the patient is well, with no evidence of recurrence of or metastasis from the tumor. The tumor arose from the leaflets and tendinous cords of the mitral valve, and was composed grossly of multiple white nodules. Histopathologic evaluation disclosed fragments composed predominantly of peripheral spindle cells in an extensive fibromyxoid stroma. The mildly pleomorphic cells of the tumor gradually blended with adjacent pieces of the mitral valvar leaflet and tendinous cords. Immunohistochemical studies revealed strong staining for vimentin, smooth muscle actin, muscle specific actin, and myoglobin, suggesting myogenic differentiation. The other patient was a 2 1/2-year-old female who died suddenly at home. Grossly and histologically, the tumor was essentially identical to the first case, and there was a 3 cm string-like extension passing into the orifice of the left coronary artery. To put the cases in context, we compare them with other descriptions of this rare type of tumor.
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PMID:Sarcoma of the mitral valve causing coronary arterial occlusion in children. 1172 10

A review of the patient files from our institution's oncology department showed that between 1950 and 2000, 11 patients were diagnosed with hemangioendothelioma of the spine, a rare, low-grade malignant vascular tumor. After reevaluation of the diagnoses by orthopaedic oncologists and pathologists, three patients were excluded; therefore eight patients formed the study group. The eight lesions were located in the thoracic (three) or lumbar spine (five, one in each vertebral level). Computed tomography scans revealed expansile lytic process. All lesions involved the vertebral body, but only one was diffuse with spinous process involvement. Treatment included: external beam irradiation alone (one patient), curettage and external beam irradiation (one patient), laminectomy and external beam irradiation (two patients), anterior resection only (two patients), and anterior resection with postoperative external beam irradiation (two patients). Patients without spinal stabilization had chronic low back pain; no patient with spinal stabilization had such pain. One patient who had surgical resection and radiation therapy had a radiation-induced sarcoma develop after 4 years. One patient who was treated with radiation therapy alone had a metastatic lung lesion develop. No other patient had tumor recurrence or progression. Therefore, patients with hemangioendothelioma of the spine may be treated with radiation therapy alone, surgery alone, or a combination thereof. However, because the number of patients in the current series was small, no definitive recommendations regarding treatment may be made. Resection of large lesions and stabilization of vertebral collapse may decrease back pain.
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PMID:Hemangioendothelioma of the spine. 1504 14

This case report describes an unusual presentation of histiocytic sarcoma in a domestic shorthair cat. Initial investigation revealed a haemodynamically insignificant hypertrophic cardiomyopathy, bronchitis and a mild irregularity of the cervical trachea. The cat's disease progressed over a two-week period. Repeat radiography and tracheoscopy revealed a marked dynamic tracheal collapse associated with a raised plaque-like lesion within the cervical trachea. Subsequent post-mortem examination and histopathology revealed disseminated histiocytic sarcoma involving the trachea and kidneys. This is the first reported case of a histiocytic sarcoma involving the trachea in either dogs or cats.
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PMID:Dynamic tracheal collapse associated with disseminated histiocytic sarcoma in a cat. 1691 Nov 15


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