Sarcoidosis mimicking lichen sclerosus.
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Diagnosis, Differential↗
Biomedical subjects
E G Levine
Publications and source records attributed to E G Levine.
Is MUGA scan necessary in patients with low-risk breast cancer before doxorubicin-based adjuvant therapy? Multiple gated acquisition.
Doxorubicin-based chemotherapy in the adjuvant treatment of breast cancer has become standard. Use of doxorubicin is limited by cardiac dysfunction; however, the incidence is dramatically reduced by limiting the dose to less than 550 mg/m(2). Although the cumulative dose in breast cancer is typically 240 mg/m(2), multiple gated acquisition (MUGA) scans are still recommended for determining cardiac functional status in these patients. To examine the need for this practice, we reviewed 296 patients who underwent surgery for breast cancer at Roswell Park Cancer Institute between July 1997 and December 1998. Fifty-nine of 95 (62%) patients receiving doxorubicin-based regimens, and 3 of 39 (7%) receiving nondoxorubicin regimens had pretreatment MUGA scans. The MUGA scans showed normal results in 58 patients and low-normal in 4 (6.5%), with no wall motion abnormalities encountered. There were no cases where doxorubicin was not used because of an abnormal MUGA scan. There were no cardiac complications in the 59 women who received doxorubicin-based chemotherapy. MUGA will screen out few, if any, women under consideration for doxorubicin-based adjuvant therapy; the decision to avoid doxorubicin can be made based on age and preexisting comorbidity. Guidelines recommending routine use of MUGA before the administration of doxorubicin for adjuvant therapy for breast cancer should be reconsidered.
Adult↗
Phase II trial of gemcitabine plus cisplatin in patients with metastatic urothelial cancer.
PURPOSE: To assess the activity and toxicity of the combination of gemcitabine and cisplatin in the treatment of chemotherapy-naive patients with metastatic urothelial cancer. PATIENTS AND METHODS: Forty-six patients with measurable stage IV carcinoma of the urothelium were enrolled onto this trial. Gemcitabine 1,000 mg/m(2) was administered intravenously for 30 to 60 minutes on days 1, 8, and 15 of each 28-day cycle. Cisplatin was administered after gemcitabine on day 1 of each cycle. The first 11 patients received an initial cisplatin dose of 100 mg/m(2). Due to the hematologic toxicity observed in several of these patients, the dose was reduced to 75 mg/m(2) in the remaining 35 patients. Patients were treated with six cycles, unless disease progression or severe toxicity necessitated earlier discontinuation. RESULTS: Ten of the 46 patients achieved a complete response and nine showed a partial response. The overall response rate was 41%. The median time to treatment failure was 5.5 months. The median survival was 14.3 months, and the 1-year survival probability was 54%. Most of the toxicities were hematologic and, in general, easily manageable. CONCLUSION: Gemcitabine plus cisplatin is active in the treatment of metastatic urothelial cancer in chemotherapy-naive patients and has an acceptable clinical safety profile. Studies are under way to further define the place of gemcitabine in combination with other chemotherapeutic agents in the treatment of metastatic urothelial cancer.
Adult↗
Phase II trial of topotecan in advanced breast cancer: a Cancer and Leukemia Group B study.
The topoisomerase I inhibitor topotecan had demonstrated good antitumor activity in several murine tumor systems and in human clonogenic assays by 1993. In that year, the Cancer and Leukemia Group B (CALGB) began a phase II trial to determine its activity in patients with breast cancer who had previously received one course of chemotherapy for advanced breast cancer. Between April 1993 and June 1994, 53 patients of performance status 0-2 entered the study, of whom 47 were eligible and 40 were evaluable. Topotecan was given at a dose of 1.5 mg/m2 over 30 minutes daily for 5 days every 21 days. In the absence of progression or withdrawal of consent, therapy was continued indefinitely. The median age was 58 years (range 30-79). There were no complete responses and four partial responses, resulting in an objective response rate of 10% (95% CI: 3-24%). Responses were noted in lymph nodes, liver, and skin. The median duration of response was 5 months. The median survival was 12 months. Life-threatening toxicities were almost exclusively hematologic. However, myelosuppression was not cumulative. It was concluded that topotecan has only modest activity among women with advanced breast cancer who have previously received one course of chemotherapy. Given its modest activity and predominant hematologic toxicity, it does not appear to be a promising drug for either single-agent or combination chemotherapy in the salvage setting of advanced breast cancer.
Adult↗
Clarification of the conceptualization and measurement of denial in psychosocial oncology research.
Denial represents an important area of study in individuals with cancer. It may be related to recognizing symptoms, seeking medical help, psychological adjustment to diagnosis and illness, and perhaps progression of the disease. However, denial has been defined theoretically and measured in a variety of ways. These differences are due to a lack of consensus as to whether denial is unconscious versus conscious, a trait versus a state, an indication of psychological disturbance versus a normal response to a life-threatening disease, or a broad versus a narrow concept. In addition, there is a lack of congruence between theoretical definitions and the operational definitions used in empirical studies investigating denial in the context of cancer. This inconsistency may be responsible for the mixed findings concerning the importance and function of denial in individuals with cancer. In this article, the ways in which denial has been conceptualized and operationalized are examined, and an overview of the research examining denial in cancer patients is provided. We recommend that future studies provide explicit definitions of denial, use multiple measures assessing different modalities and outcomes, measure denial at several times over the course of illness, and take into account aspects of the individual's situation to ensure that denial is not identified erroneously.
Adaptation, Psychological↗
Informed consent: a survey of physician outcomes and practices.
We mailed a survey to the domestic membership of the American Society of Gastrointestinal Endoscopy in an attempt to investigate how endoscopists obtained informed consent and the effect of these practices on medical malpractice claims. One thousand two hundred thirty-two (23.8%) surveys were returned. We determined that although informed consent is obtained in 98.5% of endoscopic cases, 30% of physicians leave the task of obtaining such consent to hospital or office personnel. Although endoscopists tend to be complete in terms of describing the risks of procedures to patients, all risks are not revealed equally; some complications, for example, the risk for requiring a colostomy, are disclosed by relatively few physicians, perhaps revealing a higher comfort level with a particular procedure, such as colonoscopy. Likewise, endoscopists generally explain the benefits of and alternatives to procedures, but they do not explain the more hazardous alternatives. Documentation of the informed consent process is an area in which physicians could be more thorough. Twenty-one percent of respondents had been sued, and in 42% of these instances, the informed consent process was an issue. Lawsuits in general (38%) changed the way respondents obtained consent, especially (64%) when this process had been an issue in the suit. No correlation was found between either the thoroughness of the informed consent process or the status of the person who obtained consent and the likelihood of being sued.
Communication↗
Phase I and pharmacokinetic evaluation of floxuridine/leucovorin given on the Roswell Park weekly regimen.
A phase I and pharmacokinetics study was carried out of floxuridine (FdUrd) modulated by leucovorin (LV) given on the Roswell Park regimen (LV given at 500 mg/m2 by 2-h infusion and FdUrd given by i.v. push at 1 h after the start of LV infusion, treatment being given weekly x 6). The dose-limiting toxicity was diarrhea; the MTD and recommended dose for phase II studies was 1,650 mg/m2 per week of FdUrd. The dose-response curve was steep, with 3/3 patients treated at a dose of 1,750 mg/m2 developing grade IV diarrhea. With this schedule there was no significant mucositis. Pharmacokinetic parameters showed very wide interpatient variability. Plasma decay was biphasic with a t1/2 beta of approximately 2 h. Plasma clearance was high (> 200 1 h-1). No correlation between pharmacokinetic parameters and toxicity could be identified.
Adult↗
MVAC for bladder cancer: time to move forward again.
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Antineoplastic Combined Chemotherapy Protocols↗
Leukemias and myelodysplastic syndromes secondary to drug, radiation, and environmental exposure.
The median latency of 2 degrees MDS/AL is 4 to 5 years. A high percentage of patients with 2 degrees MDS/AL convert to 2 degrees AL. Survival of either is less than 1 year. A constellation of morphologic abnormalities from all 3 cell lines produces a unique appearance. Both 2 degrees MDS and 2 degrees AL are difficult to classify by the FAB system. With the exception of the identification of karyotypic abnormalities, the biology of 2 degrees MDS/AL remains largely unexplored. Alterations of chromosomes 5 and 7 predominate, but other associated cytogenetic abnormalities are being increasingly recognized. A synthesis of data regarding 2 degrees MDS/AL resulting from the treatment of several primary malignancies generates the tentative conclusions that (a) many of the alkylating agents, and the nonclassic alkylating agent procarbazine, are leukemogens; (b) melphalan is a more potent leukemogen than cyclophosphamide. None of the other alkylating agents has been clearly established to be more or less potent than another; (c) increasing duration or amount of alkylator-based chemotherapy increases the risk of leukemogenesis; (d) low doses of radiation delivered to large volumes of bone marrow are weakly leukemogenic. High doses of radiation delivered to small volumes are not. Due to the latter, there is minimal additive risk for 2 degrees MDS/AL among studies using alkylator-based chemotherapy and radiotherapy, either concurrently or sequentially; (e) the older patient (greater than 40) is at increased risk for 2 degrees MDS/AL, at least in Hodgkin's disease. Children may be at lesser risk than adults, and younger children at lesser risk than older children; (f) the risk of 2 degrees MDS/AL peaks within the first decade after treatment for the primary malignancy. The incidence rates during the second decade are low. Identified occupational/environmental risks for 2 degrees MDS/AL include benzene, ambient and diagnostic radiation exposure, and perhaps ethylene oxide. The similarities in karyotype abnormalities among leukemic cells of those whose occupations expose them to chemical hazard, and those who are exposed to cytotoxic agents, suggest that many more environmental leukemogens have yet to be discovered. Karyotype is an important prognostic factor for both achievement of CR and for survival. Nonaggressive treatment approaches have not proven useful, although the use of hematopoietic growth factors offers promise in this area. Combination chemotherapy is justified in patients with adequate performance statuses and "favorable" karyotypes. Allogeneic bone marrow transplantation is currently the only curative approach, and can be applied without attempts to first reduce the leukemic burden.
Antineoplastic Combined Chemotherapy Protocols↗
Weight gain with breast cancer adjuvant treatment.
Available information suggests that individuals with breast cancer gain weight during adjuvant treatment and that this weight gain may be associated with poor prognosis. Exploration of the factors which affect weight gain may aid in developing weight control interventions for these patients. To determine the factors which are associated with weight gain, 32 women undergoing adjuvant chemotherapy were followed over 2 years from the beginning of adjuvant treatment. Measures of psychologic functioning and self-reports of exercise levels and eating were assessed every 2 months during the course of treatment. Sixty-nine percent of the women gained weight over treatment, resulting in a significant weight gain for the group as a whole. Weight gain was correlated positively with several psychologic measures but not with assessed biologic measures. A multiple-regression equation using psychologic/behavioural measures of emotional discharge, logical analysis, affective regulation, interpersonal sensitivity, average number of symptoms, and obsessive compulsiveness accounted for 58% of the variance in overall weight gain. At 2 years of follow-up, 27 women had gained weight for an average of 6.03 kg. The coping style of logical analysis emerged as a significant predictor of disease recurrence, accounting for 28% of the variance in weight gain at 2 years. The results are discussed in terms of identification of women likely to gain weight during adjuvant treatment, directions for future research, and development of interventions to control weight gain.
Adaptation, Psychological↗
Treatment of refractory testis cancer: salvage or savage chemotherapy?
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Antineoplastic Agents↗
Pseudodepression in hyponatremia.
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Aged↗
True histiocytic lymphoma.
It is likely that a significant number of cases of THL will continue to be misdiagnosed unless appropriate cytochemical and immunologic markers are incorporated into the panel of studies performed at diagnosis. The clinical findings are nonspecific. With the possible exception of skin infiltration, the frequency of symptoms and signs appear to approximate those of intermediate grade lymphomas. Most commonly, it is the histopathological features that suggest the histiocytic nature of a malignant process, but these alone are not sufficient to secure the diagnosis. Thus, in the absence of a clearly defined lymphoid origin, it is the detection of specific histiocytic markers that establishes a lymphoma as THL. Only the recognition and careful study of additional cases will potentially enable clinical investigators to identify any unique characteristics and distinguish this disease from other lymphomas. For the present, it would appear that the treatment indicated for a patient with diffuse large cell lymphoma would also be appropriate for a comparable patient with THL. Although long-term disease-free survival in THL is possible, there are presently inadequate data to estimate curability.
Adult↗
Sequential karyotypes in non-Hodgkin lymphoma: their nature and significance.
The examination of sequential karyotypes in hematologic disorders has demonstrated that karyotypic changes are often associated with concurrent changes in clinical behavior. Acquired abnormalities that recur among different patients may also suggest genomic areas important to tumor progression. We therefore examined sequential karyotypes in 21 patients with non-Hodgkin lymphoma (NHL). Sixteen of the 21 karyotypes demonstrated changes, including the majority of 6 small lymphocytic, 11 follicular, and 4 intermediate and high-grade diffuse lymphomas. The t(14;18)(q32;q21) occurred in ten initial karyotypes was retained in all cases. The band most frequently affected by newly acquired abnormalities was 14q32 (n = 5); chromosomes 1 and 2 (n = 5, each), and the 17p arm (n = 4) were also commonly affected. The acquired deletion of all or part of 17p appeared to be associated with a poor prognosis. Histologic transformation and karyotypic change did not correlate. This study of sequential karyotypes in NHL 1) confirms the primary importance of the t(14;18), 2) suggests that the 14q32 band is involved frequently in both primary and secondary cytogenetic events, and 3) suggests other genomic regions of potential significance to progression.
Adult↗
Treatment of refractory and relapsed Hodgkin's disease: intensive chemotherapy and autologous bone marrow or peripheral blood stem cell support.
Thirty-three patients with recurrent or refractory Hodgkin's disease were treated with high-dose cyclophosphamide, BCNU, and etoposide and supported with either autologous bone marrow or peripheral blood stem cells or both. Peripheral blood stem cells were comparable to bone marrow in supporting the recovery of hematopoiesis. Twenty-five patients (76%) were in complete remission following this therapy of whom 13 have subsequently relapsed. Twelve remain alive and disease free from 10 to 47 months. The Kaplan-Meier estimate of disease-free survival at 28 months for the entire 33 patients is 32% (95% confidence interval, 13-50%). Poor outcome in six patients was associated with bone marrow involvement by Hodgkin's disease at the time of peripheral blood stem cell collection. These six patients' survival, disease-free survival, the duration of complete remission were all significantly worse than for the 27 patients who were supported with bone marrow (n = 23), peripheral blood stem cells (n = 2), or both (n = 2), and whose marrows were free of disease at the time of stem cell collection. These data demonstrate that intensive therapy with autologous transplantation can produce extended disease-free survival for some patients with advanced Hodgkin's disease and that peripheral blood stem cell support can effectively be used for hematopoietic reconstitution. However, our observations also suggest that with this preparative regimen, bone marrow involvement at the time of peripheral blood stem cell collection is predictive for a poor outcome and alternate approaches to treatment should be considered for this subset of patients.
Adolescent↗
Cytogenetics of non-Hodgkin's lymphoma.
In the non-Hodgkin's lymphoma (NHL), recurring cytogenetic abnormalities have been identified, and significant correlations among them and morphology, immunophenotyping, and parameters of clinical outcome have been recognized. The structural involvement of the 14q32 band is substantially more frequent than are other common abnormalities, which include del(6q), i(17q), +3, +7, +12, +18, and +21. Twenty-two recurring translocations have been identified. Almost three-fourths of all breakpoints in NHL occur at sites to which lineage-determining, transformation-related genes, or fragile sites have been mapped. Besides the well-known association of the t(14;18) (q32;q21) with the follicular histologies and t(8;14)(q24;q32) with small non-cleaved cell lymphoma, several other associations between recurring cytogenetic abnormalities and morphologic subtypes have been found. Similarly, several associations between cytogenetic abnormalities and the B or T immunophenotype have been delineated. Trisomy 3 or duplications of 3p predict a favorable clinical outcome; trisomy 2 or duplication 2p and abnormalities of chromosome 17 predict a poor prognosis. Common sequential changes include a (second) 14q32 break and abnormalities of chromosomes 1 and 2. Continuing work in these areas will serve to identify more clearly those regions of the genome important to transformation, differentiation, clinical aggressiveness, and progression in NHL.
Chromosome Aberrations↗
The role of heredity in cancer.
Heredity is generally felt to play a minor role in the development of cancer. This review critically examines this assumption. Topics discussed include evidence for heritable predisposition in animals and humans; the potential importance of genetic-environmental interactions; approaches that are being used to successfully locate genes responsible for heritable predisposition; comparability of genetic findings among heritable and corresponding sporadic malignancies; and future research directions. Breast, colon, and lung cancer are used to exemplify clinical and research activity in familial cancer; clinical phenotypes, segregation and linkage analyses, models for environmental interactions with inherited traits, and molecular mechanisms of tumor development are discussed. We conclude that the contribution of heredity to the cancer burden is greater than generally accepted, and that study of heritable predisposition will continue to reveal carcinogenic mechanisms important to the development of all cancers.
Animals↗
Four new recurring translocations in non-Hodgkin lymphoma.
The identification of recurring chromosomal translocations has provided clues to the gene regions important in lymphoma development. Among 157 patients with non-Hodgkin lymphoma studied by cytogenetic analysis, four new recurring translocations have been identified--t(8;9) (q24;p13), t(11;18)(q21;q21), t(14,15)(q32;q15), and an unbalanced translocation giving rise to der(22)t(17;22) (q11;p11). Each translocation appeared twice. The t(11;18) was the only karyotypic abnormality in the two patients with it, and the t(14;15) was the sole karyotypic abnormality in one patient. All translocations were found in B-cell malignancies and were associated with both nodal and extranodal disease. Among the regions affected, only the immunoglobulin heavy-chain gene MYC, and BCL2, have thus far been associated with lymphoma. The breakpoint sites identified by these translocations warrant further investigation at the molecular level.
Aged↗