Cancer
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Tumors of the pancreas associated with extracellular mucin production include mucin-producing ductal adenocarcinoma, mucinous cystic neoplasm (MCN), and intraductal papillary mucinous tumor (IPMT). Fine-needle aspiration (FNA) is used as an adjunct to radiologic analysis for the preoperative categorization of these tumors. The current study was designed to identify distinctive cytomorphologic features that would be useful for the categorization of mucinous tumors of the pancreas. ⋯ IPMT and low-grade MCN possess distinctive cytologic features that can be used to diagnose them correctly and distinguish them from one another and from other cystic tumors. Duplication cysts closely mimic low-grade MCN, which can lead to false-positive diagnoses. Because of substantial overlap in cytologic features, mucin-producing ductal adenocarcinoma was unable to be distinguished from mucinous cystadenocarcinoma cytologically.
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Options for first-line chemotherapy in patients with metastatic colorectal carcinoma have broadened considerably with the introduction of irinotecan and oxaliplatin. Furthermore, the oral fluoropyrimidine capecitabine has demonstrated efficacy in Phase III trials and recently was approved for first-line treatment in Europe and the United States. Capecitabine yielded similar median times to disease progression and median survival rates compared with bolus 5-fluorouracil (5-FU)/leucovorin (LV) (Mayo Clinic/North Central Cancer Treatment Group regimen), with superior and similar response rates, respectively. ⋯ A randomized Phase III study comparing irinotecan and oxaliplatin in combination with the same infusional 5-FU/LV regimens and crossover in case of disease progression showed equivalent efficacy for both schedules in the first-line setting, but the irinotecan combination proved beneficial in terms of safety. New molecular targeted agents, such as angiogenesis-modulating compounds (e.g., bevacizumab) and epidermal growth factor receptor inhibitors (e.g., cetuximab), are under clinical investigation. This review updates current systemic frontline treatments and future perspectives for patients with advanced colorectal carcinoma.
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Multicenter Study Clinical Trial
Oral topotecan in children with recurrent or progressive high-grade glioma: a Phase I/II study by the German Society for Pediatric Oncology and Hematology.
Continuous oral treatment with topotecan may be more effective than the typical 1-day and 5-day treatment schedules. In previous studies of continuous treatment with topotecan, increased intestinal side effects were reported in adult patients; however, the experience in pediatric patients and patients with high-grade glioma is quite limited. ⋯ Oral topotecan (median dose, 0.9 mg/m(2) per day) administered once daily was well tolerated and somewhat effective in children with recurrent high-grade glioma. A schedule in which the daily dose is split so that dosing is performed twice daily may be superior to the current schedule.
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Although various mechanisms have been recognized as being associated with the development of resistance to imatinib mesylate in vitro and in clinical situations, their relative significance and contributions remain poorly understood, as is the sequence of events leading to the selection of the resistant phenotype. Experimental in vitro systems involving well defined cell lines and conditions can be used to some advantage to answer specific questions and to develop in vitro models of imatinib resistance that would reflect its potential heterogeneity. ⋯ BCR/ABL amplification with subsequent overexpression of Bcr/Abl protein, loss of apoptotic response, or point mutation of the ATP-binding site of BCR/ABL was associated alternatively with the acquisition of the resistant phenotype, supporting the notion that multiple mechanisms are involved in the induction of resistance to imatinib. The initial number of BCR/ABL copies itself was not related directly to the degree of resistance. The reversibility of the resistance may be complete, partial, or irreversible, depending on the mechanism(s) involved and the degree of resistance. Both cell lines serve as models for further elucidation of various aspects of imatinib-resistance mechanisms.
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Combinations of high-dose ifosfamide (IF; 10-12 g/m2) plus doxorubicin (DX; 50-90 mg/m2) have been administered to patients with advanced soft tissue sarcoma (ASTS) in an attempt to improve therapeutic efficacy. Although these combination regimens appear to yield higher response rates than do standard-dose regimens, they also are associated with significant hematologic toxicity, despite the administration of hematopoietic growth factor support. As a potentially less toxic alternative, the authors designed a sequential, dose-dense schedule of DX and IF and explored its feasibility and toxicity, as well as patient compliance with the schedule, in a Phase II trial. ⋯ Sequential administration of dose-dense DX and high-dose IF is feasible and exhibits an acceptable hematologic toxicity profile and a level of activity that is within the range described for schedules that combine high-dose IF with an anthracycline.