Reevaluation of procarbazine for the treatment of recurrent malignant central nervous system tumors

Ninety-nine patients with primary recurrent malignant tumors of the central nervous system were treated with procarbazine as a single agent. Procarbazine was not given as a specified protocol, but for patients who were ineligible or refused other protocols. All patients had been treated previously with radiotherapy and 96 patients had also received previous chemotherapy. Twenty-five patients were treated at the first progression of their tumor, 47 were treated at the second progression, and 27 were treated at the third progression of their tumor. For the aggregate, the response plus stabilization rate was 27% for glioblastoma multiforme with median time to tumor progression of 30 weeks, and 28% for other anaplastic gliomas with a median time to tumor progression of 49 weeks. With respect to the percent of patients who responded or stabilized to treatment, these results are inferior to those reported previously for patients treated with procarbazine at recurrence. With respect to duration of response and stabilization, the data are comparable.     

The 5-year results of a randomized trial of adjuvant radiation therapy after chemotherapy in breast cancer patients treated with mastectomy

The use of adjuvant radiation therapy in breast cancer patients treated with mastectomy and adjuvant chemotherapy has been controversial. In order to assess the necessity and effectiveness of adjuvant radiation therapy in this setting, we reviewed the results in 510 patients with T1-T3 tumors and pathologically positive nodes or tumors larger than 5 cm and negative nodes who were treated with adjuvant chemotherapy. Patients with four or more positive nodes or at least one positive apical node were randomized to receive either five or ten cycles of cyclophosphamide/Adriamycin (Adria Laboratories, Columbus, OH) (CA) and patients with one to three positive nodes or operable tumors larger than 5 cm and pathologically negative nodes were randomized to receive eight cycles of either cyclophosphamide, methotrexate, and 5-fluorouracil (5-FU) (CMF) or methotrexate and 5-FU (MF) chemotherapy. Two hundred six of these patients were subsequently rerandomized to receive either no further treatment or adjuvant radiotherapy. Thirty-five patients withdrew after randomization, including 34 who declined to receive radiotherapy. Radiation therapy consisted of 4,500 cGy in 5 weeks to the chest wall and appropriate draining lymph nodes. Median follow-up from chemotherapy randomization is 45 months for patients in the CA arm and 53 months for those in the CMF/MF arm. The crude rate of local failure (chest wall or draining lymph node areas) as first site of failure for patients randomized to receive chemotherapy only was 14%; for those randomized to receive both chemotherapy and radiotherapy it was 5% (P = .03). For patients in the CMF/MF arm, the rate of local failure as the first site of failure was nearly the same for patients randomized to chemotherapy only as for those randomized to adjuvant radiotherapy as well (5% v 2%). For patients in the CA arm, the crude rate of local failure was 20% for patients randomized to receive chemotherapy only, and 6% for those randomized to both types of adjuvant treatment (P = .03). Among the 43 patients treated with CA who actually received radiotherapy, there was only one local failure, compared with 12 local failures among the 59 patients (20%) who actually did not receive radiotherapy (P = .007). No significant difference was seen in disease-free survival or overall survival in either the CA or the CMF/MF arm between patients randomized to receive radiation therapy and those randomized to no further treatment.(ABSTRACT TRUNCATED AT 400 WORDS)     

Intracranial circulation: pulse-sequence considerations in three- dimensional (volume) MR angiography

The technique and feasibility of magnetic resonance (MR) angiography of intracranial vessels were studied in 35 healthy volunteers. Variations in image orientation, repetition time (TR), and flip angle were evaluated to determine their effects on flow-related enhancement. Gradient modifications--including echo time (TE), motion compensation, bandwidth, and field of view--were also studied in an effort to reduce motion-induced phase shifts. Results indicated that a FISP (fast imaging with steady precession) sequence with a TR of 50 msec, TE of 15 msec, velocity compensation in the read and section-select directions, acceleration compensation in the read direction, anisotropic volume, and a 1.25-mm partition thickness produced three-dimensional angiographic MR images that were accurate and reproducible in the depiction of the major intracranial vessels. Difficulties with field of view, persistent signal void secondary to higher-order motion, and spatial resolution remain major problems requiring additional study.     

AlphaV beta3 (αvβ3) integrin inhibition reduces leukocyte–endothelium interaction in a pressure-induced reperfusion model

The leukocyte-endothelium interaction is known to contribute to reperfusion injury, which is considered to participate in the pathophysiology of pressure ulcers, and integrin alphaV beta3 (alphavbeta3) has been shown to mediate the processes of cellular adhesion in various types of cells. This study aims to clarify leukocyte behavior in our original microcirculatory pressure-induced reperfusion model, which can visualize the microcirculation in vivo. We also estimated the effect of alphavbeta3 integrin inhibition on the reduction of the leukocyte-endothelium interaction. Mice with dorsal skinfold chambers were divided into three groups: the baseline group (n=6), in which animals received no compression; the compression-reperfusion group (n=6), in which animals underwent 2-hour compression of the dorsal skin, followed by release, and the inhibitor-treated group (n=7), in which an alphavbeta3 inhibitor, CP4715, was administered in addition to the compression-release procedure. Staining with rhodamine 6G quantitatively visualized leukocyte behavior under the intravital fluorescent microscope. Compression-reperfusion induced a significant increase in rolling, sticking, and extravasation of the leukocytes. Treatment with the inhibitor strikingly reduced leukocyte sticking and extravasation. The present experiment has provided evidence that alphavbeta3 inhibition reduces leukocyte-endothelium interaction in our original pressure-induced reperfusion model.     

Update on the treatment of polycythemia vera with recombinant interferon alfa or imatinib mesylate

Polycythemia vera is a myeloproliferative disease, which, if untreated, leads to thrombohemorrhagic complications and eventually to progressive myelofibrosis, anemia, and splenomegaly. Two newly available drugs, interferon alfa and imatinib mesylate, may alter the course of this disease. Used as single agents, each produces lasting remissions in about 75% of patients with polycythemia vera. Of significance, change in JAK2 expression has been reported after treatment with both agents.     

Extranodal lymphomas presenting as soft tissue sarcomas to a sarcoma service over a two-year period.

Non-Hodgkin's lymphoma usually presents with lymphadenopathy at multiple sites but can also involve any part of the musculoskeletal system. Occasionally the presentation is with a soft tissue mass. The presentation of large, superficial lymphomatous masses is similar both clinically and radiologically to that of soft tissue sarcomas. The six cases of lymphoma presenting to the Exeter Sarcoma Service as suspected soft tissue sarcomas, over a two-year period (2002-2004), are presented. We describe the clinical and imaging characteristics of these tumours and their subsequent management. Our cases showed variability in presentation. Only one of the six cases presented with pain and one with tenderness. Four of the cases had no lymphadenopathy and the other two had lymphadenopathy restricted to one nodal basin. Overlying soft tissue swelling occurred in four cases and in distal limb swelling beyond the mass in one case. Radiologically, lymphomas are known to be likely to exhibit confluent lymphadenopathy that is rare in patients with soft tissue sarcoma. Confluent lymphadenopathy was demonstrated in only one case of this series of patients. It is thought that lymphomas infiltrate across anatomical fascial planes more readily than sarcomas and in four of our six cases this feature was present. Clinical history, examination and MRI are insufficient to differentiate between soft tissue sarcoma and lymphoma and the importance of obtaining a pathological diagnosis prior to surgery is clear. It is crucial to differentiate lymphoma from sarcoma in order to avoid unnecessary excisional procedures in lymphoma patients.     

The impact of a patient education program on directed donations

The effect of an informational program in which the benefits and disadvantages of directed donations are discussed directly with the prospective recipient of the blood and/or that patient's family was examined during a 20-month period. Data collected for 27 regional Connecticut hospitals that accept directed donations were compared with similar data for Hartford Hospital, an 885-bed tertiary-care facility. The number of directed-donor units (68) collected by the American Red Cross Blood Services for Hartford Hospital during the study period was comparable to the number (average, 62.3) provided for smaller (301-450 beds) institutions in the state. The percentage that directed-donor units drawn for Hartford Hospital represented of the total number of homologous units provided (0.23%) was less than that for any of the categories of hospitals, by size, in the state. Supplying the patient and/or the patient's family, in a personalized manner, with information concerning the advantages and disadvantages of directed as well as of volunteer donor blood can result in a marked overall reduction in the number of directed donations and also serves to reassure those concerned about blood transfusion.     

Raf-1 kinase,epidermal growth factor receptors,and mutant ras proteins in colonic carcinomas

Epidermal growth factor receptors (EGFR) andras mutations are known to play a significant role in controlling cell growth and tumor promotion. Both of them transmit mitogenic signals to the nucleus by activation of Raf-1 kinase. In this study, the expression of EGFR and mutant Ras proteins, and, for the first time, the expression, phosphorylation and kinase activity of Raf-1 kinase have been determined in paired samples of colorectal cancer and mucosa. The tumor and mucosa samples did not differ significantly with regard to Raf-1 kinase content and activity. A major difference between tumors and mucosa was found, however, in the phosphorylation of Raf-1. Most of the mucosa samples (13/20), but only 1/20 of the cancer samples, contained hyperphosphorylated Raf-1. EGFR were significantly (p=0.0025) decreased in the tumors. The decreased phosphorylation of Raf-1 in colonic carcinomas could be the result of activation of Raf-1 phosphatases or inactivation of kinases phosphorylating Raf-1. New forms of treatment based on EGFR overexpression do not seem to be suitable for the majority of colonic cancers.This work was supported by the state of Baden-Württemberg (Verbundforschungsprojekt: Aufklärung von Mechanismen der Tumorentstehung und Tumorabwehr).