High-dose therapy and autologous hematopoietic stem-cell transplantation does not increase the risk of second neoplasms for patients with Hodgkin's lymphoma: a comparison of conventional therapy alone versus conventional therapy followed by autologous hematopoietic stem-cell transplantation.

PURPOSE: To determine the incidence of second malignancies among patients with Hodgkin's lymphoma (HL) treated with autologous hematopoietic stem cell transplantation (AHSCT) compared with patients receiving conventional therapy alone and to identify potential risk factors for their occurrence. PATIENTS AND METHODS: We analyzed data on 1,732 consecutive patients with HL treated at the British Columbia Cancer Agency from 1976 to 2001, including 202 patients undergoing AHSCT. The median follow-up duration was 9.8 years for the whole cohort, 9.7 years for those patients treated with conventional therapy, and 7.8 years from AHSCT. RESULTS: The cumulative incidence of developing any second malignancy 15 years after therapy for HL was 9% (risk ratio = 3.5; P < .001); however, the incidence did not differ between those patients receiving conventional therapy alone compared with those undergoing AHSCT (10% and 8%, respectively; P = .48). In multivariate analysis, the only factor significantly associated with an increased risk of developing any second neoplasm or solid tumor was age > or = 35 years (P < .0001). An increased risk of therapy-induced acute myeloid leukemia and therapy-induced myelodysplastic syndrome was seen for patients aged > or = 35 years (P = .03) and stage III/IV (P = .04). CONCLUSION: Patients with HL are at increased risk of developing a second neoplasm. However, those patients undergoing AHSCT do not seem to be at greater risk compared with those patients receiving conventional therapy alone, at least during the first decade after therapy.     

Direct uterine sampling with the Tao brush sampler using a liquid‐based preparation method for the detection of endometrial cancer and atypical hyperplasia

BACKGROUND.

Endometrial cytology sampling devices for direct uterine sampling have been shown in previous studies to be a reliable and relatively painless method for detecting endometrial lesions. The purpose of the current study was to determine the performance characteristics of endometrial cytology for the detection of malignancy and atypical hyperplasia using liquid‐based cytology specimens collected with the Tao brush sampler.

METHODS.

Brushings of the endometrial cavity were obtained from 139 hysterectomy specimens before routine histopathologic evaluation. Cytology specimens were fixed in PreservCyt and processed using ThinPrep technology. Cytology diagnoses were classified as nondiagnostic, negative, atypical, or positive for malignancy. Histopathologic findings were used as the gold standard for determining the performance characteristics of cytology.

RESULTS.

Histopathologic results from the 139 patients included 81 (58%) endometrial cancers, 7 (5%) complex hyperplasias with atypia, 2 (1%) complex hyperplasias without atypia, and 49 (35%) patients with benign histology. The number of specimens diagnosed cytologically as positive, atypical, negative, or nondiagnostic was 60 (43%), 40 (29%), 37 (27%), and 2 (1%) specimens, respectively. The overall sensitivity and specificity of cytology for detecting endometrial cancer and atypical hyperplasia were 95% and 66% when atypical cytology specimens were considered positive.

CONCLUSIONS.

The results of the current study indicate that direct endometrial sampling by liquid‐based endometrial cytology collected with the Tao brush sampler produces specimens that contain cellular material that may be identified as endometrial cancer or atypical hyperplasia. Both atypical and positive cytology diagnoses are indicators for triage to more specific methods of diagnosis. Cancer (Cancer Cytopathol) 2008. © 2008 American Cancer Society     

The role of econazole in the management of oculomycosis

The possible role of econazole in the management of fungal eye infections is presented in this study. An animal model of oculomycosis was used to demonstrate the efficacy of econazole in an in vivo system both as a prophylactic and as a powerful therapeutic agent against sensitive fungal pathogens. In vitro tests on 114 ocular pathogenic fungal isolates exemplified the superiority of econazole to other available imidazoles.     

Pharmacological properties of J-104132 (L-753,037), a potent, orally active, mixed ETA/ETB endothelin receptor antagonist.

J-104132 [(+)-(5S,6R, 7R)-2-butyl-7-[2-((2S)-2-carboxypropyl)-4-methoxyphenyl]-5-(3, 4-methylenedioxyphenyl)cyclopenteno[1,2-b]pyridine-6-carboxylic; also referred to as L-753,037] is a potent, selective inhibitor of ETA and ETB endothelin (ET) receptors (e.g., Ki: cloned human ETA = 0.034 nM; cloned human ETB = 0.104 nM). In both ligand-binding and isolated tissue preparation protocols, the inhibition of ET receptors with J-104132 is reversible and competitive. In vitro, J-104132 is a potent antagonist of ET-1-induced accumulation of [3H]inositol phosphates in Chinese hamster ovary cells stably expressing cloned human ETA receptors (IC50 = 0.059 nM), ET-1-induced contractions in rabbit iliac artery (pA2 = 9.70) and of BQ-3020-induced contractions in pulmonary artery (pA2 = 10.14). J-104132 is selective for ET receptors because it had no effect on contractions elicited by norepinephrine or KCl in the vascular preparations. The in vivo potency of J-104132 was assessed using challenges with exogenous ET-1. In conscious mice, 5 nmol/kg i.v. ET-1 causes death. Pretreatment with J-104132 prevents the lethal response to ET-1 when administered i.v. (ED50 = 0.045 mg/kg) or p.o. in fed animals (ED50 = 0.35 mg/kg). In conscious, normotensive rats, pressor responses to 0.5 nmol/kg i.v. ET-1 are inhibited by J-104132 after i.v. (0.1 mg/kg) or p.o. (1 mg/kg) administration. In anesthetized dogs, ET-1 was administered directly into the renal artery or brachial artery to generate dose-response (blood flow) curves, and the inhibitory potency of J-104132 (i.v. infusion) was quantified. J-104132 produced greater than 10-fold shifts in the ET-1 dose-response curves at 0.03 mg/kg/h (renal) and 0.3 mg/kg/h (brachial). Oral bioavailability of J-104132 in rats was approximately 40%. These studies indicate that J-104132 is a selective, potent, orally active antagonist of both ETA and ETB receptors and is an excellent pharmacological tool to explore the therapeutic use of a mixed ETA/ETB receptor antagonist.