A phase I-II study of continuous 5-day infusion mitomycin-C

A phase I-II study was undertaken to establish the maximum-tolerated dose of a continuous 5-day infusion of mitomycin-C and its efficacy in patients with advanced metastatic drug-resistant breast and gastrointestinal malignancies. The dose-limiting toxicity was myelosuppression, predominantly thrombocytopenia, and was severe and cumulative. Nonhematologic toxicity was infrequent, and no renal or cardiac toxicity was seen. For patients with breast cancer who had received extensive prior therapy, 3 mg/m2/day for 5 days repeated every 6-8 weeks were well-tolerated doses; and for patients with gastrointestinal cancer, the maximum-tolerated dose was 4 mg/m2/day. One patient with breast cancer had a partial response lasting 4 months, and no responses were observed in patients with gastrointestinal cancer. The administration of mitomycin-C by continuous infusion did not appear to have improved its therapeutic index.     

Treatment of advanced breast cancer with aminoglutethimide after therapy with tamoxifen

Thirty-eight metastatic breast cancer patients were treated with aminoglutethimide. All patients had progressive metastatic disease following initial response to Tamoxifen therapy. Thirty-two patients were evaluable for response, of these, two patients (6%) had complete remission, 13 patients (41%) had partial response, and six patients (19%) had stable disease. Eleven patients (34%) had progressive disease. The most common side effects were transient skin rash, lethargy or dizziness. Four patients' (11%) treatment was discontinued because of either skin rash or dizziness within the first two weeks of the study. These data show that aminoglutethimide is an effective agent following tamoxifen therapy.     

Integration of targeted therapies in gemcitabine chemotherapy regimens

Lung cancer is one of the most common malignancies in the United States and the most lethal. Non-small-cell lung cancer (NSCLC), which accounts for over 80% of all lung cancer cases, results in a particularly poor prognosis and a high mortality rate. The 5-year survival rate is still only 15%, and most patients ultimately die from this disease. Unfortunately, the therapeutic improvements resulting from the new generation of cytotoxic agents seems to have reached a plateau. Targeted therapeutics, or agents aimed at specific biologic pathways, represent a potential for great improvements in survival from this disease. Because of their greater specificity, targeted therapeutics have the potential for decreased toxicity and increased efficacy. The main categories of targeted therapies applicable for NSCLC include receptor-targeted therapy, signal transduction or cell-cycle inhibition, angiogenesis inhibition, gene therapy, and vaccines. These new agents are, in theory, more target-specific, less toxic, easier to administer, and may lead to enhanced safety and survival for patients with advanced NSCLC. Targeted therapies are in different phases of clinical testing and have shown encouraging activity as single agents or in combination with chemotherapy as well as radiation therapy. Herein we explore targeted therapy in combination with gemcitabine.     

Pathological assessment of response to induction chemotherapy in breast cancer

Macroscopic and microscopic pathology review was used to assess the degree of tumor reduction after preoperative chemotherapy in 90 patients with inflammatory and locally advanced breast cancer. Fifteen (17%) patients had no evident residual macroscopic tumor on gross pathological examination, and 6 of these 15 had no residual tumor on microscopic review either. There was no significant difference in disease-free and overall survival between the six patients with no microscopic disease and the nine patients with only microscopic residual disease but no residual macroscopic tumor. These 15 patients with major reduction after induction chemotherapy had a longer disease-free survival (DFS) (median not reached at 5 yr) than the other 75 patients with lesser degrees of tumor reduction (DFS = 22 mo; P less than 0.01). Clinical evaluation of response to chemotherapy was a less accurate predictor of outcome than was the pathological assessment of response. Complete clinical responders had a 4-yr DFS of 55%, whereas patients with non macroscopic residual tumor following preoperative chemotherapy, less than one-half of whom had been judged to be a complete clinical responder, had a median DFS of greater than 60 mo and a 4-yr DFS of 75%. Patients whose mastectomy specimen had no macroscopic residual disease had a 93% 5-yr survival compared to patients with a less marked response to therapy who had a 5-yr survival of 30% (P less than 0.01). No pretreatment patient or tumor-related variables correlated with the degree of tumor reduction following preoperative therapy. Achievement of a mastectomy specimen free of residual macroscopic tumor after preoperative chemotherapy is an excellent prognostic factor for a prolonged DFS and survival. This information should be considered in the selection of postoperative systemic therapy.     

Meniscal injuries: detection using MR imaging

Both retrospective and blinded analyses of thin-section, high-resolution magnetic resonance (MR) images of the knee joint, produced using a solenoid surface coil, indicate that MR imaging is an effective technique for evaluating meniscal injuries. Images of 49 patients were evaluated, and the results were correlated with those of subsequent arthroscopy. A grading scale was developed to rate the index of suspicion of a meniscal tear based on the MR images. Overall, approximately 80% of menisci rated grade 4 (definite tear) or 3 (probable tear) were found to have corresponding tears at arthroscopy. In many other patients with a grade 4 or 3 meniscus in whom a corresponding tear was not found arthroscopically, meniscal tears at other sites or other abnormalities were correctly diagnosed using MR. A majority of the false-positive MR images involved the posterior horns of the menisci, the sites of most false-negative arthroscopic diagnoses. The predictive value of a negative MR image was almost 100%. Even in patients with moderate-to-large effusions, the menisci were accurately evaluated. The results imply that MR imaging is useful in the preoperative evaluation of suspected meniscal tears.     

Percutaneous drainage access: a simplified coaxial technique

We describe an access technique that we have used in 150 nephrostomy and biliary drainage procedures and for access to some abscesses and viscera. The system provides safe coaxial access with a 22-gauge removable hub needle, which then acts as a guide wire and is replaced by an 18-gauge cannula. A major advantage is that only one guide wire is used (0.038-inch) for the entire drainage procedure. No significant complications have occurred to date with this method.     

Interventional radiology in the spleen

Despite the widespread use of interventional radiologic techniques, there has been reluctance to apply these to the spleen. Concern for bleeding and difficulty in negotiating around the colon and pleura have limited its use. The authors report their experience with interventional radiology of the spleen in 35 cases, including percutaneous biopsy (n = 5), diagnostic and therapeutic fluid aspiration (n = 14), and catheter drainage of abscesses (n = 9), hematomas (n = 2), intrasplenic pancreatic pseudocysts (n = 2), and necrotic tumor (n = 1). Transsplenic fluid aspiration and biopsy of the pancreas and adrenal gland were performed as well (n = 2). All procedures were performed under computed tomographic or ultrasound guidance. Biopsies were performed with 22- or 20-gauge needles only; no complications were encountered. Diagnoses included primary and secondary malignancies and an infectious process. Drainages were successful in 11 of 14 patients; pleural effusions occurred in two cases, but neither required specific therapy. Interventional radiologic procedures in the spleen are feasible, and the authors discuss methods to promote their safe application.     

Association between palmoplantar pustulosis and cigarette smoking in Brazil: a case–control study

Background  Palmoplantar pustulosis (PPP) discloses some differences compared to vulgar psoriasis (PV) in terms of age of onset, female predominance and low occurrence of psoriasis lesions elsewhere. Cigarette smoking has been associated to PPP in international studies; nevertheless, these studies were never performed among Brazilian.
Objectives  To compare prevalence of smoking among PPP, PV and other dermatologic patients (NPD).
Methods  Case–control study involving 25 PPP patients from a reference psoriasis centre. Two control groups were matched according to gender and age: 50 patients with PV and 50 NPD. Confounders were adjusted by conditional multiple logistic regression.
Results  Among cases, 84.0% were female and PPP age of disease onset (41.4 years) was greater than PV (34.5 years). Prevalence of ever smoking was higher among cases (92.0%) than PV (52.0%) and NPD (30.0%). Adjusted odds ratio of PPP ever smoking compared to PV and NPD was 9.5 and 36.2, respectively. All smokers reported the onset of their habit before the development of PPP.
Conclusions  There was significant association between PPP and smoking. However, the impact of giving it up in the clinical course of the disease remains to be established.