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Biomedical subjects

D T Sleijfer

Publications and source records attributed to D T Sleijfer.

At least 19 recordsLinked to original sources
PubMed2005

Quality of life of testicular cancer survivors and the relationship with sociodemographics, cancer-related variables, and life events.

GOALS OF WORK: The aim of this study was to (1) assess the quality of life (QoL) of testicular cancer survivors (TCSs) by comparing them to a reference group; (2) investigate the relationship between the QoL of TCSs and sociodemographics, cancer-related variables, and life events; and (3) identify TCSs at risk for an impaired QoL. PATIENTS AND METHODS: Of the TCSs approached, 50% (n=354) participated and completed a generic QoL questionnaire (RAND-36) once. Time since completion of treatment varied from 3 months to 24 years. MAIN RESULTS: (1) TCSs had significantly higher mean scores on the subscales physical functioning (p=0.02) and pain (p=0.001), but lower mean scores on mental health (p=0.04) and vitality (p<0.001) than a reference group of men. The effect sizes of these differences were small to insignificant. (2) Employment status and chronic disease were the main correlates of the QoL of TCSs. Age, negative life events, type of treatment, and the experience of a second cancer event were moderately associated with some subscales as well. (3) The joint burden of unemployment and a chronic disease was the strongest predictor for an impaired functioning. CONCLUSIONS: On a group level, TCSs experience a good QoL, but a small group appeared to be at risk for an impaired functioning, namely, those who were unemployed and had a chronic disease. The variance explained by the variables studied was low, indicating that more important predictors remain to be identified.

Activities of Daily Living↗
PubMed2005

Absence of constitutional Y chromosome AZF deletions in patients with testicular germ cell tumors.

OBJECTIVES: To investigate the frequency of azoospermia factor (AZF) deletions in Dutch patients with testicular germ cell tumors (TGCTs). Reduced fertility is associated with TGCTs and reduced fertility and TGCTs might share genetic risk factors according to the testicular dysgenesis hypothesis. Up to 8% of infertility and reduced fertility in the general male population can be explained by the presence of constitutional deletions of part of the long arm of the Y chromosome (Yq11), referred to as the AZF region. METHODS: In 112 patients with TGCT, screening for constitutional deletions in the AZF region was performed by multiplex polymerase chain reaction analysis in DNA extracted from peripheral blood lymphocytes. A set of 24 primer pairs, of which 20 primer pairs are homologous to previously identified and mapped sequenced tag sites within the AZF region were used. RESULTS: No deletions in the Yq11 region were detected in any of the 112 patients. CONCLUSIONS: Large Y chromosome microdeletions in the AZF region are not a major contributor to the development of TGCT and TGCT-associated reduced fertility.

Chromosome Deletion↗
PubMed2005

Left ventricular and cardiac autonomic function in survivors of testicular cancer.

BACKGROUND: Following cisplatin-based chemotherapy, survivors of testicular cancer have a high prevalence of cardiovascular risk factors and an increased risk of cardiovascular disease. Cardiac function has not been extensively studied and no comparisons have been made with men from the general population. DESIGN: Left ventricular and cardiac autonomic function were evaluated in chemotherapy-treated testicular cancer patients, in stage I patients after orchidectomy only, and in healthy men using Doppler echocardiography [wall motion score index, peak early (E) and atrial filling (A) velocities across the mitral valve, E/A-ratio, isovolumetric relaxation time, and deceleration time of the early peak flow] and measurements of N-terminal pro-brain natriuretic peptide and baroreflex sensitivity. Furthermore, 24-h ambulatory blood pressure was measured. RESULTS: Ninety chemotherapy-treated patients (median age 37 years, range 20-65; median follow up of 7 years, range 3-13) were compared with 44 stage I patients (median age 36 years, range 24-63) and 47 healthy controls (median age 37 years, range 22-55). Wall motion score index was less than 1.5 in all participants. Chemotherapy-treated patients had a higher peak A-wave and a lower E/A-ratio than stage I patients and controls. Isovolumetric relaxation and deceleration times did not differ between groups. Age, 24-h diastolic blood pressure and treatment with chemotherapy were significantly associated with E/A-ratio. Natriuretic peptide levels were normal. Baroreflex sensitivity was similar in the three groups. CONCLUSIONS: Chemotherapy-treated testicular cancer survivors have a lower E/A-ratio than healthy subjects from the general population, which may indicate impaired relaxation of the left ventricle and reflect the high prevalence of cardiovascular risk factors previously reported in these men.

Adult↗
PubMed2004

Endoscopic ultrasound-guided fine-needle aspiration in patients with mediastinal abnormalities and previous extrathoracic malignancy.

Enlarged mediastinal lymph nodes in patients with previous extrathoracic malignancy require pathological verification. However, surgical procedures lead to morbidity and (rarely) mortality. Endoscopic ultrasound with fine-needle aspiration (EUS-FNA) is a minimally invasive, outpatient procedure. We prospectively assessed its usefulness in patients with mediastinal abnormalities and previous extrathoracic malignancy. All patients underwent EUS-FNA prior to planned surgical procedures. Specimens were categorised as positive, negative, or inconclusive. Surgical procedures were cancelled after positive EUS-FNA. Twenty patients underwent EUS-FNA, being positive in eleven and providing an alternative diagnosis in one patient (a total of 60%). In 8 patients, EUS-FNA was negative or inconclusive, while surgery was positive in five and negative in three. Sensitivity and specificity of EUS-FNA were 69 and 100%, respectively. EUS-FNA is useful in the assessment of mediastinal abnormalities in patients with previous extrathoracic malignancy. Surgical diagnostic procedures were precluded in 60% of such patients.

Adult↗
PubMed2004

The distribution of drug-efflux pumps, P-gp, BCRP, MRP1 and MRP2, in the normal blood-testis barrier and in primary testicular tumours.

The drug-efflux pumps P-glycoprotein (P-gp) and multidrug resistance-associated protein 1 (MRP1) are present in the blood-testis barrier (BTB) and may hamper the delivery of cytotoxic drugs to the testis. The precise localisation of P-gp and MRP1 in testicular tissue and the presence of the efflux pumps MRP2 and breast cancer resistance protein (BCRP) in the BTB are unknown. We therefore studied the localisation of these pumps in the BTB in normal testis (n = 12), in non-seminoma (n = 10) seminoma (n = 10), and testicular lymphoma (n = 9). Slides were scored semi-quantitatively for P-gp, MRP1, MRP2 and BCRP and blood vessels with factor VIII antibody. In normal testis, P-gp and BCRP were strongly expressed by myoid cells and luminal capillary endothelial wall and P-gp also by Leydig cells. MRP1 was observed at the basal side of Sertoli cells and on Leydig cells. MRP2 was only weakly expressed by myoid cells. Seminomas and non-seminomas expressed P-gp and/or BCRP and/or MRP1, lymphomas strongly expressed P-gp, weakly expressed BCRP and did not or showed weak expression of MRP1. There was very little staining for MRP2 in the tumours. Newly formed vessels in all tumours only expressed P-gp and BCRP. P-gp, BCRP and MRP1 are present in different cell layers of the normal testis, suggesting the optimal protection of spermatogenesis. In germ cell tumours, this expression pattern may explain the chemoresistance observed to P-gp, BCRP and MRP1 substrates. In germ cell tumours and testicular lymphomas, P-gp and BCRP expression by tumour cells and by newly formed vessels may also contribute to chemoresistance. These findings underscore the importance of removing the affected testis in cases of primary germ cell tumours and testicular lymphomas, irrespective of whether the patient has already undergone chemotherapy.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2004

Genetic predisposition to testicular germ-cell tumours.

Testicular germ-cell tumours (TGCT) are the most common neoplasm in young men. Various studies have suggested the existence of an inherited predisposition to development of these tumours. Genome-wide screens subsequently provided evidence of a TGCT susceptibility gene on chromosome Xq27 (TGCT1) that might also predispose to cryptorchism. However, this putative gene has yet to be identified, and other TGCT susceptibility genes probably exist. Completion of the human gene map and advances in genetic research will facilitate further investigation of genetic predisposition to TGCT. Insight into inheritance of TGCT might lead to the identification of individuals at increased risk of developing the disorder, increase our understanding of the mutation pathways that lead to sporadic cases, and contribute to improvement in diagnosis and treatment. Clinicians should record the family history of cancer and urogenital differentiation defects in patients with TGCT.

Adult↗
PubMed2002

Routine chest X-rays have no additional value in the detection of relapse during routine follow-up of patients treated with chemotherapy for disseminated non-seminomatous testicular cancer.

BACKGROUND: The routine follow-up of patients with disseminated non-seminomatous testicular cancer (DNSTC) treated with the combination of orchidectomy, polychemotherapy, and if needed, resection of the residual mass, consists of regular physical examinations, chest X-rays (CXR) and tumor marker assessments. Most guidelines for this routine follow-up originate from multi-center trials. In order to estimate the value of CXR in the detection of tumor relapse after complete remission, we reviewed all patients with disseminated testicular cancer treated with chemotherapy at the University Hospital Groningen. PATIENTS AND METHODS: Three hundred and fifty-three consecutive patients with DNSTC treated between February 1977 and February 1999 at our institution were reviewed. Two hundred and ninety (82.2%) patients, who were in complete remission after cisplatin-containing chemotherapy followed by, if necessary, resection of the residual mass, entered this analysis. The follow-up schedule consisted of regular physical examinations, tumor marker assessment (lactate dehydrogenase, beta-human chorionic gonadotropin and alpha-FP) and CXR. In all patients the first diagnostic sign of tumor relapse was documented. RESULTS: During a median follow-up of 107 months (range 8-261) a tumor relapse was documented in 33 patients (11.4%). Median time to relapse was 17 months (range 6-179) after the start of chemotherapy. In 27 patients, tumor relapse was first detected by a rise in tumor markers. Two patients presented their relapse with neurological complaints. Both were diagnosed with brain metastasis. In four patients the relapse was detected by both increase in tumor markers and abnormalities in the physical examination. In none of the 33 relapsed patients was routine CXR during follow-up involved in the detection of tumor recurrence. All but one of the relapsed patients had elevated tumor markers before the start of chemotherapy. The total number of CXR made during follow-up in all 290 patients was 10 160; none were diagnostic for the detected relapses. CONCLUSIONS: These data suggest that routine CXR has no additional value in the detection of tumor relapses during follow-up after chemotherapy in the subset of patients who present their DNSTC with increased tumor markers and are in complete remission after treatment. In order to save valuable resources, CXR can be omitted from the follow-up schedule after chemotherapy for marker-positive non-seminomatous testicular cancer in complete remission.

Adolescent↗
PubMed2001

Prospective evaluation of early cardiac damage induced by epirubicin-containing adjuvant chemotherapy and locoregional radiotherapy in breast cancer patients.

PURPOSE: To evaluate prospectively the cardiotoxic effects of epirubicin-containing adjuvant chemotherapy in breast cancer patients. PATIENTS AND METHODS: Patients (median age, 46 years; range, 28 to 55 years) were treated with five cycles of fluorouracil, epirubicin (90 mg/m2), and cyclophosphamide (FEC) (group I, n = 21) or with four cycles of FEC followed by high-dose chemotherapy consisting of cyclophosphamide, thiotepa, and carboplatin (group II, n = 19). Locoregional radiotherapy was applied subsequently. Cardiac evaluation was performed before chemotherapy (T0), 1 month after chemotherapy, 1 month after radiotherapy (T2), and 1 year after start of chemotherapy (T3). Left ventricular ejection fraction (LVEF) was determined by radionuclide ventriculography and diastolic function by echocardiography. Autonomic function was assessed by 24-hour ECG registration for heart rate variability (HRV) analysis. Time-corrected QT (QTc) was assessed and N-terminal atrial natriuretic peptide (NT-ANP) and brain natriuretic peptide (BNP) were measured as biochemical markers of cardiac dysfunction. RESULTS: No patient developed overt congestive heart failure (CHF) and the mean LVEF declined from 0.61 at T0 to 0.54 at T3 (P =.001), resulting in an LVEF below 0.50 (range, 0.42 to 0.49) in 17% of the patients, whereas 28% had a decline of more than 0.10. Plasma NT-ANP levels increased gradually from 237 pmol/L at T0 to 347 pmol/L at T3 (P <.01), whereas plasma BNP levels increased from 2.9 pmol/L to 5.1 pmol/L (P =.04). Mean QTc increased from 406 msec at T0 to 423 msec at T3 (P <.01). No persistent alterations were found in diastolic function and HRV. CONCLUSION: Relatively low doses of epirubicin in adjuvant chemotherapy for breast cancer results in mild subclinical myocardial damage demonstrated by a decline in LVEF, an increase in natriuretic peptide levels, and an increase in QTc, which may indicate a long-term risk of CHF.

Adult↗
PubMed2001

Improved long term survival of patients with metastatic nonseminomatous testicular germ cell carcinoma in relation to prognostic classification systems during the cisplatin era.

BACKGROUND: The current study reviews chronologic changes in the long term outcome of patients with metastatic nonseminomatous testicular germ cell tumors (NSTGCT) who were treated at a single institution during the past two decades. The 10-year survival of prognostic subgroups according to the classification of the International Germ Cell Consensus Classification Group (IGCCCG) and various other prognostic classifications is examined in time to evaluate whether cumulative experience has led to an improved outcome of patients with metastatic NSTGCT and to explore differences in outcome of prognostic subgroups. METHODS: Two hundred ninety-nine patients with metastatic NSTGCT who were treated with cisplatin-based polychemotherapy during the period from 1977 to 1996 were staged retrospectively according to the Royal Marsden (RM) classification and the following prognostic classifications: IGCCCG, Indiana, Medical Research Council (MRC), and European Organization for Research and Treatment of Cancer (EORTC). The numbers of patients who were treated during the periods 1977-1986 and 1987-1996 were 146 and 153, respectively. Survival curves were constructed using the Kaplan-Meier method, and disease specific 10-year survival rates of prognostic subgroups treated during the two consecutive 10-year periods were compared using the log rank test. RESULTS: The median follow-up of surviving patients during the periods 1977-1986 and 1987-1996 was 14.7 years (range, 0.2-20.6 years) and 7.0 years (range, 0.4-11.4 years), respectively. The actuarial disease specific 10-year survival rate of patients with metastatic NSTGCT increased from 76% during the period 1977-1986 to 88% during the period 1987-1996 (relative risk [RR], 0.51; 95% confidence interval [95% CI], 0.29-0.89; P < 0.05). The 10-year survival rates of patients with good, intermediate, and poor prognoses according to the IGCCCG classification were 95%, 74%, and 37%, respectively, during the period 1977-1986 and 94%, 87%, and 66%, respectively, during the period 1987-1996. Patients with a poor prognosis according to the IGCCCG classification showed the greatest increase in 10-year survival (RR, 0.43; 95% CI, 0.18-1.04; P = 0.06). Analysis using the RM, Indiana, and EORTC classifications also showed an improved 10-year survival rate of patients with a poor prognosis who were treated during 1987-1996 compared with those who were treated during 1977-1986. CONCLUSIONS: The 10-year survival rate of patients with metastatic NSTGCT who were treated with cisplatin-based chemotherapy significantly increased from 76% during the period 1977-1986 to 88% during the period 1987-1996. This improvement during the cisplatin era resulted mainly from an increase in the survival of patients with metastatic disease who had a poor prognosis. These results indicate that the management of patients with NSTGCT is still improving.

Adolescent↗
PubMed2001

Treatment of cancer in old age, shortcomings and challenges.

The burden of cancer in old age is increasing as a result from both the expanding number of older persons in the population and the high and still increasing cancer incidence in this group. The goal of this article is to outline the shortcomings and challenges of the management of cancer in the elderly. Several factors contribute to the complexity of this management, such as the enormous heterogeneity in this population, increased co-morbidity, reduced functional status, increased frailty and different treatment goals from those in younger patients. Other problems include the lack of data on the efficacy and toxicity of cancer treatment in this age group, the lack of awareness of life-expectancy and the lack of an easy applicable and validated frailty scale. Improvement of the quality of oncological care in this age group could be achieved by initiation of clinical trials specifically directed at the elderly, in which a frailty scale is implemented. The results of these trials may lead to more evidence-based decision making in cancer treatment in the elderly.

Activities of Daily Living↗
PubMed2001

Dose-finding and pharmacological study of ifosfamide in combination with paclitaxel and carboplatin in resistant small-cell lung cancer.

BACKGROUND: To find the maximum tolerated dose for ifosfamide in combination with paclitaxel and carboplatin in small-cell lung cancer patients (SCLC), who are resistant to cyclophosphamide, doxorubicin and etoposide (CDE). PATIENTS AND METHODS: Different dose schedules of ifosfamide were combined with fixed doses of paclitaxel 175 mg/m2 and carboplatin AUC 6 mg/ml min. Included were 30 patients, with a median age of 60 years, and median time off prior cytotoxic treatment of 8 weeks. All patients were previously treated with CDE and 11 had received re-induction CDE. RESULTS: Dose limiting toxicity of our schedule was persistent thrombocytopenia. None of the patients developed neutropenic fever. Non-haematological toxicity was mild, although two treatment-related deaths occurred. Fifty-four percent of patients had a partial response and median survival time was twenty-five weeks. CONCLUSIONS: The maximum tolerated dose of this combination for patients with resistant SCLC is ifosfamide 2000 mg/m2 in combination with paclitaxel 175 mg/m2 and carboplatin AUC 6 mg/ml min administered on the first day of a 21-day cycle.

Adult↗
PubMed2001

Sexual functioning after treatment for testicular cancer--review and meta-analysis of 36 empirical studies between 1975-2000.

Literature concerning sexual functioning after treatment for testicular cancer from 1975-2000 is reviewed. After a literature search in Medline and Psylit was conducted, as well as a search for cross-references made, a meta-analysis was performed. To describe sexual functioning, several aspects of the sexual response cycle were used: sexual desire, sexual arousal, erection, and orgasm; ejaculatory function, sexual activity, and sexual satisfaction were used as well. The number of patients included in the studies as well as treatment modalities were taken into account. A total of 36 relevant studies was screened (28 retrospective and 7 prospective studies), concerning 2,786 cases of testicular cancer. Meta-analysis revealed that ejaculatory dysfunction was reported most frequently and was related to surgery in the retroperitoneal area. Erectile dysfunction was related to irradiation, but was reported least frequently. Other sexual functions were not related to treatment modality. Meta-analysis revealed no deterioration of sexual functioning in the course of time, except a decrease in sexual desire and an increase in sexual satisfaction. Retrospective studies reported more sexual dysfunction than did prospective studies. Detailed analysis of separate studies, however, revealed a wide variation in reported sexual morbidity, as well as in assessment methods. Somatic consequences of disease and treatment may reduce ejaculation; however, other aspects of sexual functioning are not clearly related to disease- or treatment-related factors and may instead refer to a psychological vulnerability caused by one's confrontation with a life-threatening, genito-urinary disease, such as testicular cancer.

Erectile Dysfunction↗
PubMed2001

Long-term haematological recovery following high-dose chemotherapy with autologous bone marrow transplantation or peripheral stem cell transplantation in patients with solid tumours.

long-term peripheral blood counts and factors influencing long-term trilineage haematological recovery of consecutive patients in a single institution treated with high-dose chemotherapy (hdc) and abmt or psct for solid tumours were examined. patients with a relapse-free survival of >1 year were included in the analysis (n = 131). Peripheral blood counts were examined 6 months and yearly following transplantation. Median follow-up was 4.1 years (range 1-10+ years). Three years after transplantation 91% of patients had normal white blood counts (WBC), 94% normal haemoglobin (Hb) and 75% normal platelets. Trilineage recovery was complete in 70% (n = 83) at 3 years and 85% (n = 50) at 5 years. Recovery of Hb occurred before WBC and platelet recovery. Approximately 25% of patients displayed an elevated MCV throughout the follow-up period. These long-term results were independent of age, high-dose regimen, number of reinfused stem cells and stem cell source. Double (n = 12) vs single (n = 119) transplantations showed significantly slower trilineage recovery and higher MCV. No secondary graft failure, myelodysplasia or leukaemia was encountered. In conclusion, complete trilineage recovery after HDC followed by ABMT or PSCT occurs slowly. PSCT and ABMT are capable of maintaining long-term haematopoiesis. Slower recovery is seen after double transplantations. The results suggest lasting implications for bone marrow function after autologous transplantation.

Adult↗
PubMed2001

Adsorptive voltametry to determine platinum levels in plasma from testicular cancer patients treated with cisplatin.

Patients cured of metastatic testicular cancer with cisplatin chemotherapy may suffer late adverse effects even after 20 years. The cause of these late adverse effects has not been elucidated yet. One cause might be prolonged tissue retention of platinum in these patients. Therefore, an extremely sensitive method for measuring platinum in plasma was used to investigate whether platinum is still detectable in plasma 10 to 20 years after cisplatin chemotherapy. High-pressure decomposition of plasma is followed by adsorptive voltametric determination of platinum, with a limit of quantification of 6 pg/g plasma. This procedure appeared suitable for the measurement of platinum in 44 former patients with platinum levels ranging from 22 to 140 pg/g plasma. This method is approximately 6000 times more sensitive than the standard flameless atomic absorption spectrophotometry (AAS) method. The platinum levels of these 44 patients were significantly elevated when compared with 20 control patients who were cured of testicular cancer but did not receive cisplatin chemotherapy (p < 0.001). There was a significant correlation between plasma platinum concentrations and follow-up time after cisplatin administration (r = -0.658, p < 0.001). This study shows that patients with testicular cancer who were treated with cisplatin can retain platinum in their body for at least 20 years. More data are needed to investigate whether there is a relation between the prolonged retention of platinum and long-term toxicity.

Adolescent↗
PubMed2001

Management of chemotherapy-induced adverse effects in the treatment of colorectal cancer.

The anticancer agents fluorouracil, raltitrexed, irinotecan and oxaliplatin show limited efficacy in the treatment of colorectal cancer and may be associated with substantial toxicity. Therefore, the prevention and reduction of chemotherapy-induced adverse effects is of major significance, in accordance with the increasing concern for the quality of life of patients with cancer. Therapeutic drug monitoring of fluorouracil and chronomodulation of fluorouracil and oxaliplatin, have been effective in reducing the incidence and gravity of adverse effects in several clinical trials. However, these concepts have not been implemented in clinical practice yet. At the present time, dose adaptation and supportive measures are the main tools for toxicity control in the treatment of colorectal cancer. In this review, supportive measures for alleviation of the adverse effects of fluorouracil, raltitrexed, irinotecan and oxaliplatin, respectively, are described, based on study results. The main adverse effects of these agents are myelosuppression, oral mucositis, diarrhoea, acute cholinergic syndrome, nausea and emesis, neurotoxicity, hand-foot syndrome and other cutaneous adverse effects, ocular toxicity, cardiotoxicity, small bowel toxicity, asthenia, elevated liver transaminase levels and alopecia. The incidence and gravity of these adverse effects are more or less related to the agent and administration schedule involved. The supportive measures and recommendations include the use of specific drugs, alterations of administration schedule and several nonpharmacological methods. In addition, guidelines for dosage adjustments when toxicity occurs are presented. For optimal management of adverse effects, patients should be considered individually, while patients, nurses and physicians should cooperate to identify and treat adverse effects in an early stage of their development.

Antineoplastic Agents↗