New antimetabolites in the treatment of human malignancies.

Several new antimetabolites have been evaluated in clinical trials in recent years. Those with the most promising activity include the structurally related purine analogs fludarabine, 2-chlorodeoxyadenosine, and 2'-deoxycoformycin. These compounds have shown impressive activity against a broad spectrum of indolent lymphoproliferative disorders, including hairy-cell leukemia, chronic lymphocytic leukemia, and low-grade non-Hodgkin's lymphomas. They may also be useful in the treatment of acute leukemias. In contrast, they lack activity against common solid tumors. They have been generally well tolerated in large clinical trials; however, each of them is myelosuppressive and immunosuppressive. It is unlikely that any one of these drugs, when used as a single agent, will provide optimal therapy for any disease other than, possibly, hairy-cell leukemia. Combinations with other cytotoxic agents and biologics are in development, and perhaps they will lead to more effective regimens in the future.     

Philadelphia chromosome (Ph1)-associated leukemias: A family study

In the present study we describe a family in which a mother and her son developed leukemia in close temporal proximity. The boy presented with a clinical picture consistent with acute lymphoblastic leukemia. His mother developed chronic myelogenous leukemia. Using Giemsa banding we demonstrated that both cases had an associated Philadelphia chromosome. Hematologic, cytogenetic, and HLA haplotyping studies were performed, but did not reveal a genetic basis for the high incidence of leukemia in this family.     

Urinary cytodiagnostic abnormalities in 50 patients with non-Hodgkin's lymphomas

Urinary cytodiagnostic evaluation was performed on 50 consecutive patients with non-Hodgkin's lymphomas. In 14 patients (28%) the urine sediment contained characteristic lymphoma cells. The groups with or without a positive urine cytology were comparable with respect to type of lymphoma, stage and course of disease, and recent treatment with chemotherapy. However, those with a positive urine cytology were more likely to have clinical evidence of kidney disease (43% vs 8%), although this was rarely attributed to disseminated lymphoma. In fact, in three patients, a positive urine cytology was the sole or presenting evidence for disseminated lymphoma. Although the groups with or without a positive cytology were similar with regard to physicochemical urinary findings, there were marked differences in the frequency of microscopic abnormalities. All patients with a positive cytology had evidence of renal parenchymal necrosis, renal tubular injury, or pathologic cast formation as compared with only 56% of those with a negative cytology. Thus, urinary cytodiagnostic evaluation may provide an important adjunct in the staging and evaluation of patients with malignant lymphomas.     

Intraluminal calcifications in the small bowel of newborn infants with total colonic aganglionosis

Intraluminal calcifications were found in the small bowel of 4 newborns with total colonic aganglionosis. Abdominal radiography demonstrated circular aggregations of small punctate calcific densities in the right lower quadrant and evidence of bowel obstruction. There was a microcolon in each case. The calcifications, which resemble those seen in small intestinal atresia and stenosis, are probably related to fetal intestinal stasis, and may be differentiated from those due to meconium peritonitis.     

Magnetic resonance imaging of the brainstem: normal structure and basic functional anatomy

Normal structure and basic functional anatomy of the brainstem were studied using anatomic sections obtained with a cryomicrotome whole-organ sectioning technique. Major tracts and nuclei were identified and their function summarized. Magnetic resonance imaging of the brainstem was performed on 10 normal volunteers. By comparing these images with the corresponding anatomic sections, normal structures, including major tracts and nuclei, were identified. Knowledge of location and function of clinically important brainstem nuclei and tracts is necessary for optimal magnetic resonance image interpretation.     

Quality-of-life assessment in cancer treatment protocols: research issues in protocol development.

BACKGROUND: Interest in incorporating quality of life as an end point in clinical studies of cancer treatment has intensified in recent years. PURPOSE: We provide practical suggestions that will assist investigators considering including quality-of-life assessment in phase III therapeutic trials. METHODS: We discuss issues important in study planning, including quality-of-life definition, priority studies for quality-of-life assessment, eligibility requirements, and design. CONCLUSIONS: Many of the problems that quality-of-life studies have encountered, from protocol approval to data analysis, could be addressed and alleviated during protocol development. This discussion is intended to assist and stimulate investigators conducting research in this area.     

Iron chelation: a potential therapeutic strategy in oesophageal cancer

Raised intracellular iron has been identified as a potential aetiological factor in the development of several epithelial malignancies, including those of the gastrointestinal tract. The mechanism behind this increase is thought to include disorders of iron uptake and storage. Several iron chelators have been identified as potential anti-tumour agents, with much work undertaken to ascertain the exact mode of action. Despite this, there is little known about the role that these drugs play in the cellular iron metabolism of oesophageal cancer. Consequently, the present study looks to review the relationship of two clinically important iron-chelating agents, deferoxamine and deferasirox, on cellular iron uptake and storage in oesophageal squamous and adenocarcinoma. This provides important evidence for the debate about the role these agents have in the clinical management of such tumours.

Linked Article

This article is a commentary on Ford et al., pp. 1316–1328 of this issue. To view this paper visit http://dx.doi.org/10.1111/bph.12045