Use of the humanized anti-epidermal growth factor receptor monoclonal antibody h-R3 in combination with radiotherapy in the treatment of locally advanced head and neck cancer patients.

PURPOSE: To evaluate safety and preliminary efficacy of the humanized anti-epidermal growth factor receptor monoclonal antibody h-R3 in combination with radiotherapy (RT) in unresectable head and neck cancer patients. Secondary end points were the measurement of h-R3 serum levels and the assessment of the potential mechanisms of antitumor effect on patient biopsies. Anti-idiotypic response to h-R3 was assessed. To predict pharmacologic effect, a mathematical model for antibodies recognizing antigens expressed in tumors and normal tissues was built. PATIENTS AND METHODS: Twenty-four patients with advanced carcinomas of the head and neck received six once-weekly infusions of h-R3 at four dose levels in combination with RT. Pretreatment tumor biopsies were obtained to evaluate epidermal growth factor receptor expression as an enrollment criterion. Second biopsies were taken to evaluate the proliferative activity and angiogenesis in comparison with the pretreatment samples. Patient serum samples were collected to measure h-R3 levels and anti-idiotypic response. RESULTS: The combination of h-R3 and RT was well tolerated. Antibody-related adverse events consisted in infusion reactions. No skin or allergic toxicity appeared. Overall survival significantly increased after the use of the higher antibody doses. Immunohistochemistry studies of tumor specimens before and after treatment revealed that antitumor response correlated with antiproliferative and antiangiogenic effect. One patient developed antibodies to h-R3. The mathematical model predicted that the maximum difference between the area under the curve in tumors and normal tissues is reached when the antibody has intermediate affinity. CONCLUSION: h-R3 is a well-tolerated drug that may enhance radiocurability of unresectable head and neck neoplasms.     

The importance of angiogenesis in ovarian cancer

Advanced stage ovarian cancer has a high rate of recurrence even after surgery followed by chemotherapy combining carboplatin and a taxane. New strategies are currently under way to combat this situation and one of the most promising ones is based on the knowledge that angiogenesis, the mechanism of formation of new blood vessels coupled with the degradation of the extracellular matrix for metalloproteinases, could be crucial in the development of this tumor. The principal molecule implicated in angiogenesis process of ovarian cancer is the vascular endothelial growth factor (VEGF). Several studies are now in progress to clarify its role as a diagnostic tool or its therapeutic implication. Presently, there is no indication for the use of VEGF in a preliminary diagnosis seeing that an increase in levels can be seen in both benign and malignant ovarian conditions. VEGF is also responsible for an increase in vascular permeability and is directly related to symptoms such as ascites and pleural effusion, both of which are frequent in ovarian cancer. Several papers have analised the role of VEGF as a prognostic factor and some of them do confirm VEGF as an independent prognostic factor in ovarian cancer. VEGF and the metalloproteinase system coupled with angiogenesis are currently being evaluated as therapeutic targets but no positive results have yet to be seen in this field.      

Experimental validation tests of fast Fourier transform convolution and multigrid superposition algorithms for dose calculation in low-density media.

BACKGROUND AND PURPOSE: Modern conformal radiotherapy treatments require accurate dose calculation in any relevant clinical situation. One of these situations is the treatment of lung tumors, where irradiation has to be planned under challenging conditions for dose calculation. In this study we assess the errors in dose values predicted by fast Fourier transform convolution (FFTC) and multigrid superposition (MGS) algorithms implemented in a commercial treatment planning system (TPS). MATERIALS AND METHODS: FFTC and MGS algorithms were used in a FOCUS 3.0.0 (Computerized Medical Systems, USA) to calculate doses in treatment plans using photon beams of 6 and 25 MV nominal energy from a Saturne 43 linac (GE Medical Systems, USA). A 10x10-cm beam irradiating a mediastinum-lung and a thoracic wall-lung-thoracic wall modeled geometry was assessed. The calculated data were compared with measurements performed with radiographic films and ionization chamber. RESULTS: FFTC algorithm leads to an average deviation from ionometric dose measurements of over 10%. Discrepancies between measured and calculated beam fringe values (distance between 50 and 90% isodose lines) of up to 8 mm were observed. For MGS algorithm, all the points assessed in both geometries fulfilled the 3%-3 mm accuracy criteria and the average deviation of absolute dose was about 1%. A maximum of 3 mm deviation in the beam fringe for any depth was found and was within 2 mm beyond the buildup region. Deviations between ionometric and film measurements were within 3%. CONCLUSIONS: MGS algorithm assesses with reasonable accuracy dose distributions and absolute dose in inhomogeneous regions like the lung region. Therefore, and respecting the inhomogeneity dose calculation, the system could be used in routine clinical practice and in dose-escalation programs. This is not true in the case of FFTC algorithm which leads to errors greater than 10% in the absolute dose calculation and underestimates the beam fringe by up to 8 mm.     

Intravenous Leiomyomatosis of the Uterus

Three cases of intravenous leiomyomatosis (IVL) of the uterus, a rare benign smooth-muscle tumor, are described. A preoperative diagnosis of IVL was not made in any of the patients, all of which presented with a pelvic mass with the presumptive diagnosis of leiomyoma. Surgical exploration confirmed the presence of uterine mass and two of the three cases showed extra-uterine extension into the ovarian or uterine veins. Histological examination demonstrated a fascicular pattern of bland spindle-shaped smooth-muscle cells, which extended to veins inside the myometrium or to extrauterine veins. This was confirmed by immunohistochemical stain for desmin and factor VIII. Despite their histological benignity, these lesions have a tendency to metastasize and are closely related to the conditions called “benign metastasizing leiomyoma” and “intracaval mass and cardiac extension”. The primary treatment of IVL is hysterectomy and excision of any extrauterine tumor, when technically feasible. Anti-estrogenic therapy has been suggested as potentially useful in controlling of unresectable tumor. According to the literature, the follow-up must be long and periodic postoperative ultrasonic or magnetic nuclear resonance imaging studies may be useful in detecting growth of residual intravascular tumor.     

A comprehensive review of the natural history of Helicobacter pylori infection in children

Across populations of children, Helicobacter pylori prevalence ranges from under 10% to over 80%. Low prevalence occurs in the U.S., Canada, and northern and western Europe; high prevalence occurs in India, Africa, Latin America, and eastern Europe. Risk factors include socioeconomic status, household crowding, ethnicity, migration from high prevalence regions, and infection status of family members. H. pylori infection is not associated with specific symptoms in children; however, it is consistently associated with antral gastritis, although its clinical significance is unclear. Duodenal ulcers associated with H. pylori are seldom seen in children under 10 years of age. H. pylori-infected children demonstrate a chronic, macrophagic, and monocytic inflammatory cell infiltrate and a lack of neutrophils, as compared with the response observed in adults. The effect of H. pylori infection on acid secretion in children remains poorly defined. The events that occur during H. pylori colonization in children should be studied more thoroughly and should include urease activity, motility, chemotaxis, adherence, and downregulation of the host response. The importance of virulence determinants described as relevant for disease during H. pylori infection has not been extensively studied in children. Highly sensitive and specific methods for the detection of H. pylori in children are needed, especially in younger pediatric populations in which colonization is in its early phases. Criteria for the use of eradication treatment in H. pylori-infected children need to be established. Multicenter pediatric studies should focus on the identification of risk factors, which can be used as prognostic indicators for the development of gastroduodenal disease later in life.     

Reduction of atherosclerosis in cholesterol-fed rabbits and decrease of expressions of intracellular adhesion molecule-1 and vascular endothelial growth factor in foam cells by a water-soluble fraction of Polygonum multiflorum

Polygonum multiflorum stilbeneglycoside （PMS） is a water-soluble fraction of Polygonum multiflorum Thunb. , one of the most famous tonic traditional Chinese medicines, that has protective effects on the cardiovascular system. The purpose of the present study is to elucidate the effects of PMS on macrophage-derived foam cell functions and the reduction of severity of atherosclerosis in hypercholesterolemic New Zealand White （NZW） rabbits. NZW rabbits were fed for 12 weeks with a normal diet, a high cholesterol diet, or a high cholesterol diet associated with irrigation with different doses of PMS （25, 50, or 100 mg/kg）. Treatment of NZW rabbits fed with high cholesterol diet with 100 mg/kg PMS attenuated the increase in plasma cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, and plasma triglyceride. Treatment with 50 and 100 mg/kg PMS caused 43% and 60% decrease in atherosclerotic lesioned area ratio to total surface area, respectively. In U937 foam cells, PMS could decrease the high expression of intercellular adhesion molecule （ICAM）-1 protein and the vascular endothelial growth factor （VEGF） protein levels in the medium induced by oxidized lipoprotein when analyzed by flow cytometry. The results proved that PMS is a powerful agent against atherosclerosis and that PMS action could possibly be through the inhibition of the expression of ICAM-1 and VEGF in foam cells.     

Effects of single dose, postinduction dexamethasone on recovery after cardiac surgery

BACKGROUND: Corticosteroids have been recommended to facilitate rapid recovery after cardiac surgery. We previously reported that dexamethasone given after induction of anesthesia decreases the incidence of postoperative shivering. We performed a post hoc analysis of the data obtained during that study, focusing on secondary outcomes. METHODS: A total of 235 adult patients undergoing elective coronary or valvular heart surgery were randomized to receive dexamethasone 0.6 mg/kg or placebo after induction of anesthesia. Patients who had pharmacologically treated diabetes mellitus, had hypersensitivity to dexamethasone, or were receiving treatment with corticosteroids were excluded. RESULTS: We found that, compared with placebo, patients receiving dexamethasone were more likely to remain tracheally intubated for 6 hours or less (26.4% vs 10.0%, p = 0.020) and had a lower incidence of early postoperative fever (20.2% vs 36.8%, p = 0.009) and new-onset atrial fibrillation during the first 3 days postoperatively (18.9% vs 32.3%, p = 0.027). However, we could not demonstrate a statistical difference in the intensive care unit or hospital length of stay, or in overall morbidity and mortality. The dexamethasone-treated patients were also more likely to have a higher blood glucose on admission to the intensive care unit (186 mg/dL vs 143 mg/dL, p = 0.012). CONCLUSIONS: Dexamethasone facilitates early tracheal extubation and is associated with a lower incidence of early postoperative fever and new-onset atrial fibrillation. Apart from a treatable decreased glucose tolerance, dexamethasone treatment was not shown to affect morbidity or mortality significantly.