[Role of the morning report in the training of internists].
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Humans↗
Biomedical subjects
D T Sleijfer
Publications and source records attributed to D T Sleijfer.
Treatment-associated leukemia following testicular cancer.
BACKGROUND: Men with testicular cancer are at an increased risk of leukemia, but the relationship to prior treatments is not well characterized. The purpose of our study was to describe the risk of leukemia following radiotherapy and chemotherapy for testicular cancer. METHODS: Within a population-based cohort of 18 567 patients diagnosed with testicular cancer (from 1970 through 1993), a case-control study of leukemia was undertaken. Radiation dose to active bone marrow and type and cumulative amount of cytotoxic drugs were compared between 36 men who developed leukemia and 106 matched control patients without leukemia. Conditional logistic regression was used to estimate the relative risk of leukemia associated with specific treatments. All P values are two-sided. RESULTS: Radiotherapy (mean dose to active bone marrow, 12.6 Gy) without chemotherapy was associated with a threefold elevated risk of leukemia. Risk increased with increasing dose of radiation to active bone marrow (P for trend =.02), with patients receiving radiotherapy to the chest as well as to the abdominal/pelvic fields accounting for much of the risk at higher doses. Radiation dose to active bone marrow and the cumulative dose of cisplatin (P for trend =.001) were both predictive of excess leukemia risk in a model adjusted for all treatment variables. The estimated relative risk of leukemia at a cumulative dose of 650 mg cisplatin, which is commonly administered in current testicular cancer treatment regimens, was 3.2 (95% confidence interval = 1.5-8.4); larger doses (1000 mg) were linked with statistically significant sixfold increased risks. CONCLUSIONS: Past treatments for testicular cancer are associated with an increased risk of leukemia, with evidence for dose-response relationships for both radiotherapy and cisplatin-based chemotherapy. Statistically nonsignificant excesses are estimated for current radiotherapy regimens limited to the abdomen and pelvis: Among 10 000 patients given a treatment dose of 25 Gy and followed for 15 years, an excess of nine leukemias is predicted; cisplatin-based chemotherapy (dose, 650 mg) might result in 16 cases of leukemia. The survival advantage provided by current radiotherapy and chemotherapy regimens for testicular cancer far exceeds the small absolute risk of leukemia.
Adult↗
Erectile dysfunction with chemotherapy.
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Adult↗
Circulating plasma platinum more than 10 years after cisplatin treatment for testicular cancer.
We have shown in patients cured from metastatic testicular cancer that up to 20 years after administration of cisplatin-containing chemotherapy, circulating platinum is still detectable in plasma. This finding may influence the development of long-term, treatment-related side-effects.
Adolescent↗
Role of metallothionein in cisplatin sensitivity of germ-cell tumours.
Cisplatin (CDDP) is an extremely active drug in the treatment of germ-cell tumours. Earlier, we found an unexpected inverse correlation between the total amount of sulfhydryl groups and CDDP sensitivity in a panel of 3 human germ-cell-tumour and 3 colon-carcinoma cell lines. Major components of the sulfhydryl groups are glutathione and metallothionein (MT). We further investigated a possible role of MT in the CDDP sensitivity of germ-cell tumours. MT levels and functionality of the germ-cell-tumour and colon-carcinoma cell lines were found to be inversely correlated with CDDP sensitivity. No difference in sub-cellular localization of MT could be observed among the types of cell lines. In agreement with the in vitro data, immunohistochemical detection of MT was high in 11/14 primary human germ-cell tumours and low in 7/7 human colon carcinomas. MT-protein expression in primary germ-cell tumours did not discriminate between responding and non-responding patients. As compared with the primary tumours, MT-protein expression decreased in 5/7 post-chemotherapy residual vital tumours or remained undetectable (2/7). MT-protein expression in the germ-cell tumours was not related to total p53-protein expression. In summary, over-expression of MT was found in germ-cell tumours, both in cell lines and in human tumours. Although MT-protein over-expression seems to be associated with the CDDP sensitivity of germ-cell tumours, MT-protein expression in primary germ-cell tumours did not differ between responding and non-responding patients and therefore cannot be used to predict response to chemotherapy.
Antineoplastic Agents↗
Long-term chemotherapy-related cardiovascular morbidity.
As a consequence of the successful use of chemotherapy in the treatment of curable neoplasms such as germ cell tumours and malignant lymphomas, and the increasing application of primary and adjuvant chemotherapy for various tumour types, the number of patients with a prolonged life expectancy after treatment is rising. Attention to long-term side-effects, including cardiovascular toxicity, is therefore of growing importance. In this review we evaluate the literature on long-term cardiovascular toxicity related to chemotherapy in adult patients. Two categories of patient with favourable life expectancy have been reviewed, namely patients cured of metastatic disease by chemotherapy and patients treated with adjuvant chemotherapy. In the first category, the literature on long-term cardiovascular morbidity in survivors of metastatic testicular cancer and lymphomas is discussed, while in the second category this is done for patients treated with adjuvant chemotherapy for breast and colon cancer. As well as the direct toxic effects of chemotherapy on the cardiovascular system, the indirect toxic effects such as chemotherapy-related metabolic changes that may cause cardiovascular morbidity are also discussed.
Adult↗
A young female with an endodermal sinus tumor in a pericardial localized cyst.
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Adult↗
The effects of a postgraduate course on opioid-prescribing patterns of general practitioners.
BACKGROUND: The objective of this study is to evaluate whether a single palliative cancer care workshop, which included information about drug prescribing, had an effect on the opioid-prescription patterns of general practitioners in daily practice. METHOD: The opioid-prescription figures of 68 general practitioners who had participated in the workshop were aggregated from the computer system of the Regional Sick Fund. The prescription figures of a year before and a year after the workshop were compared and a control group of non-participants was included. RESULTS: This study showed a limited efficacy of a palliative cancer care workshop on the morphine-prescription figures of the general practitioners in daily practice. This limited effect did not accord with the results of a pre- and post-workshop questionnaire evaluating the attitudes of the same practitioners. CONCLUSION: A single workshop can not effectuate substantial changes in prescription behaviors. Possibilities for more reinforcements are discussed.
Drug Utilization↗
Retroperitoneal metastases in testicular cancer: role of CT measurements of residual masses in decision making for resection after chemotherapy.
PURPOSE: To determine the relative importance of computed tomographic (CT) measurements for the prediction of histologic findings in residual masses in patients with nonseminomatous testicular cancer. MATERIALS AND METHODS: Measurements of the maximum transverse size of retroperitoneal metastases before and after chemotherapy were available in 641 patients who underwent resection after chemotherapy while their levels of tumor markers were normal. Radiologic measurements of mass size and clinical characteristics (histologic findings in primary tumor and levels of alpha-fetoprotein, human chorionic gonadotropin, and lactate dehydrogenase before chemotherapy) were related to histologic findings in the residual mass with logistic regression analysis. RESULTS: At resection, 302 patients had benign tissue, and 339 had residual tumor (mature teratomas or cancer). Tumor was more frequent in larger masses after chemotherapy but was unrelated to mass size before chemotherapy. Inclusion of the reduction in size significantly improved the logistic regression model, which included mass size after chemotherapy. This model was further improved with the addition of clinical characteristics. Areas under the receiver operating characteristic curves increased from 0.74 to 0.77 and 0.83 with these models. CONCLUSION: A small retroperitoneal mass after chemotherapy is an important predictor of benign histologic findings in residual masses in patients with nonseminomatous testicular cancer. However, better predictions can be made when the reduction in size and clinical characteristics are considered as well. Decisions regarding resection should be based on the combination of these characteristics rather than on only mass size after chemotherapy.
Area Under Curve↗
Cardiovascular morbidity in long-term survivors of metastatic testicular cancer.
PURPOSE: To determine whether long-term survivors of metastatic testicular cancer have an increased risk of cardiovascular morbidity more than 10 years after chemotherapy. PATIENTS AND METHODS: Eighty-seven patients treated with cisplatin-containing chemotherapy before 1987 who were in remission for at least 10 years and whose ages were </= 50 years at the time of analysis were evaluated for the occurrence of cardiovascular events. Sixty-two of 87 patients were additionally evaluated for cardiac damage and cardiovascular risk factors. Their cardiovascular risk profile was compared with that of 40 patients with comparable age and follow-up duration treated with orchidectomy only for stage I disease. RESULTS: Major cardiac events were found in five (6%) of the 87 patients (age at time of event, 30 to 42 years; time after chemotherapy, 9 to 16 years): two with myocardial infarction and three with angina pectoris with proven myocardial ischemia. An increased observed-to-expected ratio of 7.1 (95% confidence interval, 1.9 to 18.3) for coronary artery disease, as compared with the general male Dutch population, was found. In addition, one patient experienced a cerebrovascular accident. Exercise ECG did not reveal cases of subclinical coronary artery disease. Echocardiography showed normal systolic left ventricular function in most patients, but diastolic left ventricular function was disturbed in 33% of the patients. Of 62 chemotherapy patients, 79% had hypercholesterolemia, 39% had hypertension, 25% still experienced Raynaud's phenomenon, and 22% had microalbuminuria. Compared with patients with stage I disease, the chemotherapy patients had higher blood pressure and higher total cholesterol and triglyceride levels and were more insulin-resistant. CONCLUSION: In long-term survivors of metastatic testicular cancer, we observed a significantly increased risk for occurrence of cardiac events accompanied by a persisting unfavorable cardiovascular risk profile. Accurate follow-up, focused on cardiovascular complications and aimed at intervention in these young cancer survivors, seems to be important.
Adult↗
Risk factors determining chemotherapeutic toxicity in patients with advanced colorectal cancer.
Antitumour therapy in advanced colorectal cancer has limited efficacy. For decades, fluorouracil has been the main anticancer drug for the treatment of colorectal cancer. Recently, however, new agents have been introduced: raltitrexed, irinotecan and oxaliplatin. Currently, the dosage for an individual patient is calculated from the estimated body surface area of the patient. Toxicity, however, frequently necessitates decreasing the dosage, extending the dose interval or even discontinuing treatment. Risk factors with predictive value for toxicity have been identified in several studies. These risk factors are often determined by the pharmacokinetic and pharmacodynamic properties of the drug. In this review, the risk factors for toxicity of the cytotoxic agents used in the treatment of advanced colorectal cancer are considered. For fluorouracil, age, gender, performance status, genetic polymorphism of dihydropyridine dehydrogenase, drug administration schedule, circadian rhythm of plasma concentrations, history of previous chemotherapy-related diarrhoea, xerostomia, low neutrophil levels, and drug-drug interactions have been identified as affecting chemotherapeutic toxicity. For raltitrexed, gender and renal and hepatic impairment, and for oxaliplatin, renal impairment and circadian rhythm of plasma concentrations, respectively, can be considered as risk factors for toxicity. In addition, age, performance status, bilirubinaemia, genetic polymorphism of uridine 5'-diphosphate-glucuronyltransferase-1A1 and drug administration schedule have been shown to be related to irinotecan toxicity. The available literature suggests that dose adjustment based on these risk factors can be used to individualise the dose in order to decrease toxicity and to improve the therapeutic index. This also applies to therapeutic drug monitoring, which has been shown to be effective controlling the toxicity of fluorouracil in some studies. Future research is warranted to assess the potential advantage of dose individualisation of chemotherapy founded on risk factors, over direct dose calculation from the estimated body surface area, with regard to toxicity, therapeutic index, and quality of life, in patients with advanced colorectal cancer.
Antineoplastic Agents↗
[Dyspnea in cancer: causes and symptomatic treatment].
Dyspnoea is a frequent symptom in advanced cancer patients. The control of breathing can be impaired by different mental and physical factors that may coincide and change over time. Apart from the treatment of specific pathophysiologic causes, symptomatic management is of utmost importance. Only few controlled trials evaluating the efficacy of symptomatic treatment of dyspnoea in advanced cancer patients are available. There is evidence that systemically administered opioids are effective in alleviating breathlessness in patients with cancer.
Adrenal Cortex Hormones↗
Loss of the Y-chromosome in the primary metastasis of a male sex cord stromal tumor: pathogenetic implications.
The first published chromosomal pattern of the retroperitoneal lymph node metastasis of a malignant gonadal stroma cell tumor of the adult testis is presented. Karyotyping showed structural chromosomal abnormalities and loss of the Y-chromosome. This loss was confirmed in primary tumor and metastasis using fluorescence in situ hybridization (FISH). The characteristic chromosomal abnormality of adult testicular germ cell tumors, an i(12p), was not present. The results are compared with other data of testicular and ovarian sex cord stromal tumors. From the comparison of the male tumors, it is concluded that loss of the Y-chromosome might have a pathogenetic significance.
Chromosome Deletion↗
Surgery versus surveillance in stage I non-seminoma testicular cancer.
Today, the standard treatment for patients with clinical Stage I non-seminomatous testicular germ cell tumors (NSTGCT) following orchidectomy is either primary retroperitoneal lymph node dissection (RPLND) or close surveillance with cisplatin-based polychemotherapy in case of a relapse. Both treatment modalities provide excellent overall survival rates up to 100%. Consequently, selection of the most appropriate management option is not primarily guided by survival considerations. The choice between the available options, each having its merits and its drawbacks, should be made based on a number of factors including treatment-related morbidity, views and expertise of the physician, patient preferences, the expected degree of patient compliance, and prognostic factor analysis. To date, the role of adjuvant chemotherapy as an alternative management option for patients with clinical Stage I NSTGCT at high risk of occult metastases is limited. This systemic treatment modality would be a realistic alternative if the reliability of prognostic factors to identify high-risk Stage I patients could be improved. This review addresses relevant issues in the management of patients with clinical Stage I NSTGCT to provide information that will allow a rational selection of the most appropriate management option.
Antineoplastic Combined Chemotherapy Protocols↗
Cytogenetic analysis of a mature teratoma and a yolk sac tumor component of a late relapse of a disseminated testicular nonseminoma.
We report on the cytogenetics of a primary testicular nonseminoma, a residual mature teratoma after remission-induction chemotherapy, and a late relapse after 9 years of follow-up, in one patient. The late relapse was composed of a mature teratoma and a yolk sac tumor component. Cytogenetic comparison of the different tumors shows that progression of primary testicular nonseminoma to residual mature teratoma and to a late-relapse lesion is accompanied by net loss of chromosomes. In addition, our findings may suggest that transformation to viable cancer in a late-relapse lesion is accompanied by further chromosomal losses.
Adult↗
Long-term results of preoperative intra-arterial doxorubicin combined with neoadjuvant radiotherapy, followed by extensive surgical resection for locally advanced soft tissue sarcomas of the extremities.
BACKGROUND AND PURPOSE: In the 1980s a combined modality therapy of intraarterial doxorubicin, neoadjuvant radiotherapy and surgery was initiated at the Groningen University Hospital as a limb-saving treatment for locally advanced, primarily irresectable high-grade soft tissue sarcomas (STS) of the extremities. This study presents the short- and long-term results. PATIENTS AND METHODS: Between 1983 and 1987, 11 patients were treated with intraarterial doxorubicin, preoperative radiotherapy (10 x 3.5 Gy) and surgical resection. Non-radical resections received additional postoperative radiotherapy of 20-30 Gy. RESULTS: The limb-salvage rate was 91%, without local recurrences during a median follow-up of 84 months. Six patients died (55%); five from metastatic disease (45%). There were five long-term survivors with a median follow-up of 10 years. Three patients (60%) suffered serious late complications, resulting in disabilitating limb function. CONCLUSION: Although this approach is feasible as a limb-saving treatment for these unfavorable STS, long-term morbidity is high.
Adult↗
Objectives for an internship internal medicine: from the Dutch Blueprint (Raamplan 1994) to implementation into a practical logbook.
BACKGROUND: The Dutch Blueprint 1994 (Raamplan 1994) describes the objectives of undergraduate medical education. The Blueprint, developed in order to improve medical education in the Netherlands, is accepted by all Dutch medical schools and has been legislated. AIM: Translation of global objectives of the Blueprint into specific requirements of a Logbook (guideline and evaluation tool) for the internship Internal Medicine. DESCRIPTION: The Blueprint as such is impracticable as a guideline during the Internal Medicine internship. The content covers the objectives for the entire field of medicine, and the volume dedicated to Internal Medicine is too large to fit in with a twelve week internship. The practicability of the Blueprint leaves much to be desired because it is complex, and not easily accessible. So, the Blueprint was adapted on three points: (1) selecting those objectives out of the whole content, which are specifically relevant to Internal Medicine; (2) decreasing the volume Internal Medicine by clustering and defining the requirements; (3) making the Logbook usable as a guideline and evaluation instrument. CONCLUSION: The Logbook is a good starting-point to evaluate whether students meet the objectives of the Blueprint related to the discipline Internal Medicine.
Education, Medical, Graduate↗
Medical oncology in the next century.
Medical oncology is a relatively young, rapidly growing subspecialty of internal medicine. This discipline will increasingly fulfil a role in the multidisciplinary approach for cancer patients. The fact that the population is rapidly aging, makes it of relevance to train medical oncologists further in the treatment of elderly patients. The growing number of cancer survivors deserves also special attention in order to limit the frequency of long-term side effects. Apart from the classical function as a doctor who treats cancer patients with drugs, the medical oncologist will play an expanding role at the far ends of oncology, namely in prevention and palliative care. Basic sciences create a tremendous amount of new knowledge on cancer detection, behavior and rational drug design. An important task for the medical oncologist will be to translate this expertise to the clinical scenario. The expanding requirement of specific skills of medical oncologists in the next century is likely to cause a further subspecialization within medical oncology.
Cancer Care Facilities↗