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H J Hoekstra

Publications and source records attributed to H J Hoekstra.

At least 37 records · Page 2Linked to original sources
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

Radiation therapy following lymph node dissection in melanoma patients: treatment, outcome and complications.

Adjuvant radiation treatment following lymph node dissection in the melanoma patient has been suggested and investigated in an attempt to gain regional control and improve survival. In this review we discussed the treatment, the loco-regional control, disease-free and survival rates and complications. Historically melanoma has been thought of as a relatively radioresistant tumour. Nowadays, radiation delivered according to the hypofractionated schedule is the most used, although there are no data to confirm that this schedule improves the therapeutic impact. Almost all the reviewed studies were retrospective, which could have led to an underestimation of the true incidence of the treatment toxicity and morbidity. Adjuvant radiotherapy after lymph node dissection for metastases of melanoma seems to improve loco-regional control without improving overall survival. The available data indicate the need for improved regional control rates in patients with extranodal extension, multiple involved nodes (more than three) and patients with large involved nodes (larger than 3 cm). The complications seem manageable and consist mainly of fibrosis and edema.

Disease-Free Survival↗
PubMed2004

Treatment-related upper limb morbidity 1 year after sentinel lymph node biopsy or axillary lymph node dissection for stage I or II breast cancer.

BACKGROUND: In a prospective study, upper limb morbidity and perceived disability/activities of daily life (ADLs) were assessed before and 1 year after sentinel lymph node biopsy (SLNB) or axillary lymph node dissection (ALND). METHODS: A total of 204 patients with stage I/II breast cancer (mean age, 55.6 years; SD, 11.6 years) entered the study, and 189 patients (93%) could be evaluated after 1 year. Fifty-eight patients (31%) underwent only SLNB, and 131 (69%) underwent ALND. Assessments performed before surgery (t(0)) and 1 year after surgery (t(1)), included pain, shoulder range of motion, muscle strength, upper arm/forearm circumference, and perceived shoulder disability/ADL. RESULTS: Considerable treatment-related upper limb morbidity was observed. Significant (P < .05) changes between t(0) and t(1) were found in all assessments except strength of elbow flexors. Patients in the ALND group showed significantly more changes in the range of motion in forward flexion, abduction, and abduction/external rotation; grip strength and strength of shoulder abductors; circumference of upper arm and forearm; and perceived shoulder disability in ADLs compared with the SLNB group. Multivariate linear regression analysis showed that ALND could predict a decrease of range of motion in forward flexion, abduction, strength of shoulder abductors, grip strength, and shoulder-related ADLs and an increase in the circumference of the upper arm. Radiation of the axilla (19 patients) predicts an additional decrease in shoulder range of motion. CONCLUSIONS: One year after treatment of breast cancer, there is significantly less upper limb morbidity after SLNB compared with ALND. ALND is a predictor for upper limb morbidity.

Activities of Daily Living↗
PubMed2004

Chemotherapy affects the pattern of failure after shear loading of the proximal tibial growth plate.

INTRODUCTION: Tibial bones are shorter and less resistant to shear forces after treatment with doxorubicin, methotrexate, or cisplatin. We investigated the pattern of failure after shear loading of the proximal tibial growth plate in rats treated with these chemotherapeutic agents. MATERIALS AND METHODS: Male Wistar rats from the age of 4 weeks were given doxorubicin intravenously at 15 mg/m2 body surface area (BSA), methotrexate 60 mg/m2 BSA, or cisplatin 7.5 mg/m2 BSA. There was one nontreated control group fed ad libitum an d a diet control group for each drug-treated group. At the age of 13 weeks the tibial bones were dissected. The proximal growth plate was shear loaded to failure in the posteroanterior direction. The pattern of failure through the growth plate was examined. RESULTS: In rats fed ad libitum the failure pattern ran mainly through the transitional zone between proliferating and hypertrophic chondrocytes, but the pattern of failure showed considerable variability. The pattern in rats treated with methotrexate or cisplatin and that in their diet controls were comparable. In rats treated with doxorubicin the fracture ran mainly through the trabecular zone. CONCLUSIONS: Doxorubicin affects the pattern of failure after shear loading of the proximal tibial growth plate, but methotrexate and cisplatin do not. Special attention should be paid to epiphyseal injuries in children treated with doxorubicin.

Animals↗
PubMed2004

Quality of life of survivors of testicular germ cell cancer: a review of the literature.

GOALS OF WORK: Testicular cancer (TC) affects young men in the prime of life. The excellent prognosis and an increasing incidence have led to a growing number of testicular cancer survivors (TCSs). The aim of this review was to summarize and discuss research findings on the quality of life (QOL) of TCSs in terms of physical, psychological, and social well-being. PATIENTS AND METHODS: Literature databases were used to identify studies published between 1980 and 2003. A quality assessment using methodological and treatment-related criteria was performed to distinguish stronger- from poorer-quality studies. MAIN RESULTS: Twenty-three studies met the inclusion criteria. Quality assessment showed that seven studies were qualitatively stronger. The majority of TCSs in both stronger and poorer quality studies reported a good QOL. Prospective and retrospective studies showed that QOL after completion of treatment increased and negative consequences of TC on life decreased compared to the situation directly after diagnosis. The stronger-quality studies reported mainly on physical and psychological well-being but did not examine social well-being and the impact of treatment-related characteristics comprehensively. CONCLUSIONS: Both stronger- and poorer-quality studies indicate that the majority of TCSs experience a good QOL, but the shortcomings on both the methodological and content level prevent us from drawing such a conclusion. Additional research with strong designs is needed to gain clearer insight into the QOL of TCSs as a group and of individuals at risk for physical, psychological, and social problems.

Adaptation, Psychological↗
PubMed2004

The value of FDG-PET in the detection, grading and response to therapy of soft tissue and bone sarcomas; a systematic review and meta-analysis.

BACKGROUND: Sarcomas represent a significant diagnostic and therapeutic challenge that requires techniques to provide better assessment of the disease than provided by traditional means. FDG-PET depicts the increased metabolism in abnormal tissues, enabling visualisation and quantification in vivo. The objective of this review was to assess the diagnostic value of FDG-PET in the detection, grading and therapy response of soft tissue and bone sarcomas. METHODS: A systematic review and meta-analysis of clinical studies on FDG-PET and sarcomas was conducted. Databases of PubMed, Embase and Cochrane were searched for studies. Besides that, the references of identified studies were reviewed. Three reviewers independently assessed the methodological quality. Statistical pooling was possible for studies concerning detection and grading of studies with mixed sarcomas (soft tissue and bone) and studies with soft tissue sarcomas only. RESULTS: Twenty-nine studies met the inclusion criteria. There was disagreement between the reviewers in 21.5% of the questions from the criteria list. The methodological quality of most of the included studies was poor. Pooled sensitivity, specificity and accuracy of PET for the detection of sarcomas were 0.91, 0.85 and 0.88, respectively. The difference between the mean Standard Uptake Value (SUV) in malignant and benign tumours for the studies concerning mixed and soft tissue sarcomas was statistically significant, as well as the difference in FDG uptake between low and high grade mixed sarcomas. CONCLUSIONS: The meta-analysis in this study was limited by the fact that only a few studies had mutual comparable outcome parameters. Moreover, the methodological quality of the studies was generally poor. Nevertheless, our results indicate that FDG-PET can discriminate between sarcomas and benign tumours and low and high grade sarcomas based on the mean SUV. The diagnostic implications of these results have to be investigated, especially the discrimination between benign tumours and low grade sarcomas. Based on this meta-analysis, there is no indication to use FDG-PET in the standard treatment of sarcomas. In the future PET imaging in bone and soft tissue sarcomas should be directed to the clinical implication for the detection and grading of sarcomas and the treatment evaluation of locally advanced sarcomas.

Adolescent↗
PubMed2004

Microalbuminuria, decreased fibrinolysis, and inflammation as early signs of atherosclerosis in long-term survivors of disseminated testicular cancer.

Testicular cancer patients have an increased risk for coronary artery disease more than ten years after cisplatin-based chemotherapy. We investigated whether vascular changes, including endothelial dysfunction, are present earlier. Ninety chemotherapy-treated testicular cancer patients (median follow-up of seven years) were compared with 44 patients after orchidectomy only and 47 healthy men. Microalbuminuria was present in 10 (12%) chemotherapy patients, one stage I patient and none of the controls. Chemotherapy patients had higher levels of fibrinogen, C-reactive protein (hs-CRP), von Willebrand factor (vWF), plasminogen activator inhibitor (PAI-1), and tissue-type plasminogen activator (t-PA). Chemotherapy patients with elevated PAI-1 (25/90) showed clustering of cardiovascular risk factors resembling the metabolic syndrome. In conclusion, cured testicular cancer patients showed a high prevalence of microalbuminuria and increased plasma levels of endothelial and inflammatory marker proteins, which might progress to more severe endothelial dysfunction and overt atherosclerosis.

Adult↗
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↗
PubMed2004

Continuously infused carboplatin used as radiosensitizer in locally unresectable non-small-cell lung cancer: a multicenter phase III study.

PURPOSE: To determine the radiosensitizing effect of prolonged exposure of carboplatin in patients with locally unresectable non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with histologically proven NSCLC, performance score <2, weight loss <10%, and normal organ functions were randomized between carboplatin 840 mg/m2 administered continuously during 6 weeks of radiotherapy or thoracic radiotherapy alone (both 60 Gy). Toxicity was evaluated with National Cancer Institute Common Toxicity Criteria (NCI CTC) and the Radiation Therapy Oncology Group (RTOG) criteria. Quality of life was measured with European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30/LC13 questionnaires. RESULTS: One-hundred and sixty patients were included. Pathologically confirmed persistent tumor was present in 53% of patients in the combination arm versus 58% in the radiotherapy alone arm (P=0.5). Median survival in the combination arm was 11.8 [95% confidence interval (CI) 9.3-14.2] months and in the radiotherapy alone arm 11.7 (95% CI 8.1-15.5) months; progression-free survival was not different between arms [6.8 and 7.5 months, respectively (P=0.28)]. Acute toxicity was mild, late toxicity was radiation-induced cardiomyopathy (three patients) and pulmonary fibrosis (five patients). Quality of life was not different between arms, but in all measured patients cough and dyspnea improved, pain became less, and slight paresthesia developed 3 months after treatment. CONCLUSION: Addition of continuously administered carboplatin as radiosensitizer for locally unresectable NSCLC does not improve local tumor control or overall survival.

Carcinoma, Non-Small-Cell Lung↗
PubMed2004

Doxorubicin potentiates TRAIL cytotoxicity and apoptosis and can overcome TRAIL-resistance in rhabdomyosarcoma cells.

Doxorubicin (DOX) and ifosfamide (IFO) are the most active single agents in soft tissue sarcomas (STS). Tumour necrosis factor-alpha (TNF-alpha) is used for STS in the setting of isolated limb perfusions. Like TNF-alpha, TNF-related apoptosis-inducing ligand (TRAIL) induces apoptosis. In contrast to TNF-alpha preliminary studies suggest that TRAIL lacks systemic side effects. The effects of TRAIL alone and in combination with DOX or 4-hydroxy-IFO were evaluated in the TNF-alpha sensitive rhabdomyosarcoma cell line KYM-1, its 5-fold TNF-alpha sensitive subline KD4 and its >150-fold TNF-alpha resistant subline 37B8R. Membrane expression of TRAIL-receptors DR4 (death receptor 4), DR5 (pro-apoptotic), DcR1 (decoy receptor 1), DcR2 (anti-apoptotic) was assessed by flow cytometry. Cytotoxicity was determined by microculture tetrazolium assays. Apoptosis assays were performed with acridine orange. DOX (doxorubicin) and 4-OH-IFO decreased survival in all cell lines; a 2-fold resistance was observed for both drugs in 37B8R. All cell lines expressed DR4 and DR5, but hardly any DcR1 or DcR2. TRAIL was cytotoxic in KYM-1, even more in KD4 and induced massive apoptosis; 37B8R was >500-fold resistant to TRAIL and little apoptosis could be observed. TRAIL plus DOX showed synergistic cytotoxicity in KYM-1 and 37B8R. TRAIL plus 4-OH-IFO showed addition in all three cell lines. DOX plus TRAIL-induced more cytotoxicity and apoptosis in all cell lines compared to TRAIL alone. In 37B8R, DOX overcame resistance to TRAIL. In KYM-1, KD4 and 37B8R, sensitivity and resistance to TNF-alpha and TRAIL parallels. TRAIL-resistance was independent from expression of TRAIL-receptors. DOX with TRAIL could overcome TRAIL-resistance in 37B8R cells.

Antineoplastic Agents↗
PubMed2003

The management of clear cell sarcoma.

Clear cell sarcoma is a rare soft tissue tumour, constituting approximately 1% of all soft tissue sarcomas. Prognosis is reported to be poor due to the great propensity to metastasise regionally and distantly. In this paper, we report the surgical experience of two university hospitals. Both disease-free and overall survival after resection of clear cell sarcoma in this limited study were excellent, which may be explained by relatively small tumour size in seven out of eight patients and adjuvant radiation treatment. The current treatment for clear cell sarcoma is wide local tumour excision, with adjuvant radiation therapy for resection margins of less than 1 mm.

Adolescent↗
PubMed2003

Fluorodeoxyglucose-positron emission tomography and sentinel lymph node biopsy in staging primary cutaneous melanoma.

AIM: We report the value of sentinel lymph node (SLN) biopsy and fluorodeoxyglucose-positron emission tomography (FDG-PET) in relation to SLN biopsy in staging primary cutaneous melanoma. METHODS: Fifty-five patients with primary cutaneous melanoma >1.0 mm. Breslow thickness and no palpable regional lymph nodes underwent a FDG-PET scan before SLN biopsy. RESULTS: SLN's were retrieved in 53 patients. Melanoma metastases were found in the SLN of 13 patients. FDG-PET detected the lymph node metastases in two of the 13 patients with SLN metastases. In five patients FDG accumulation was recorded in a regional lymph node basin, while no tumour positive SLN was found. In eight patients FDG-PET showed increased activity at a site of possible distant metastasis. Metastatic disease was confirmed in one patient. No explanation for the positive FDG-PET result could be found in five cases. CONCLUSION: FDG-PET should not be considered in this group. SLN biopsy reveals regional metastases that are too small to be detected by FDG-PET. The prevalence of distant metastases is too small to justify routine use of FDG-PET.

Adolescent↗
PubMed2003

Expression of multidrug resistance proteins, P-gp, MRP1 and LRP, in soft tissue sarcomas analysed according to their histological type and grade.

The biological behaviour of different histological types and grades of soft tissue sarcomas (STS) varies. This might result in a differing sensitivity to cytotoxic drugs. Cross-resistance to functionally and structurally distinct natural-product drugs, known as multidrug resistance (MDR), is associated with the overexpression of P-glycoprotein (P-gp), multidrug resistance-associated protein 1 (MRP1) and lung resistance-related protein (LRP). The purpose of this study was to evaluate the expression of P-gp, MRP1 and LRP in STS according to their histological type and grade. In 141 chemotherapy-naive STS patients, the expression of the three MDR proteins was detected by immunohistochemistry. Nine histological types were documented. These were 19% grade 1, 34% grade 2 and 47% grade 3 tumours. Expression of P-gp and LRP was observed more frequently than the expression of MRP1 (P<0.0001). P-gp expression was most pronounced in malignant fibrous histiocytoma (MFH), but was low in leiomyosarcomas. MRP1 was expressed in most malignant peripheral nerve sheath tumours (MPNST). LRP was strongly expressed in MFH and unspecified sarcomas, but was low in liposarcomas. MRP1 and LRP expression was significantly more common in grades 2 and 3 compared with grade 1 tumours. P-gp expression was correlated with MRP1, especially in grade 3 STS. In conclusion, P-gp, MRP1 and LRP are expressed in the majority of STS, but this expression varies according to the histological type. MRP1 and LRP, but not P-gp expression, were found to be correlated to tumour grade. MDR might contribute to the observed differences in clinical behaviour within the heterogeneous group of STS.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed2003

The effect of chemotherapy on the morphology of the growth plate and metaphysis of the growing skeleton.

AIM: To establish the effect of three single chemotherapeutic agents on the growing skeleton, male Wistar rats were studied. METHODS: From the age of 4 weeks the rats were given iv doxorubicin (DOX) 15 mg/m(2) body surface area (BSA), methotrexate (MTX) 60 mg/m(2) BSA or cisplatin (CDDP) 7.5 mg/m(2) BSA. One non-treated control group was fed ad libitum (ad lib) and for every drug-treated group there was a diet-control group. After dissection at 13 weeks of age, morphology of the proximal tibial growth plate and metaphysis were studied. RESULTS: Compared to the ad lib group, DOX significantly decreased and MTX increased growth plate height (P<0.05). CDDP decreased height of the proliferating layer (P<0.05). Trabecular volume was decreased in the DOX and CDDP treated rats compared to the ad lib group (P=0.054). Compared to the diet control group trabecular bone volume was unaffected in the DOX group and decreased in the MTX and CDDP group (P<0.05). CONCLUSIONS: Doxorubicin causes growth plate thinning, methotrexate increases growth plate height and cisplatin does not affect growth plate height. All three chemotherapeutic agents decrease the trabecular volume of the proximal tibial metaphysis. Part of the effect of DOX, MTX and CDDP is related to the treatment induced malnutrition.

Animals↗
PubMed2003

Late morbidity after treatment of breast cancer in relation to daily activities and quality of life: a systematic review.

AIMS: Breast cancer treatment may result in long-term upper limb morbidity: reduced range of motion of the shoulder, muscle weakness of the arm and hand, lymph edema, pain and numbness. Relationship of this late morbidity with activities of daily life (ADL) and quality of life (QOL) is infrequently described and the strength of this relationship is not clear. METHODS: A systematic review was performed to evaluate the results of studies, analyzing late morbidity of breast cancer treatment in relationship with ADL and/or QOL. A literature search over the last 20 years (1980-2000) was performed in the databases MEDLINE, EMBASE, PSYCHLIT and CANCERLIT. Methodological quality of selected articles was assessed and additional, aspects of treatment related late morbidity and the relationship to ADL and/or QOL were summarized. RESULTS: From the 1642 yielded articles 15 fulfilled our primary selection criteria. Only six articles could be selected due to the inappropriate methodological quality. There was high variation in prevalence of pain (12-51%), impairments in range of motion (2-51%), edema (6-43%) and decreased muscle strength (17-33%). Four articles reported significant relationships between late morbidity of the upper limb and perceived disabilities in ADL/QOL. The strength of these relationships was rather low. CONCLUSIONS: Few studies investigated the relationship between late morbidity of the upper limb after treatment of early breast cancer and ADL/QOL. Significant relationship between late morbidity and restrictions of daily activities and poorer QOL was reported, however, the strength of this relationship was rather low.

Activities of Daily Living↗
PubMed2003

Expression of multidrug resistance-associated proteins in rhabdomyosarcomas before and after chemotherapy: the relationship between lung resistance-related protein (LRP) and differentiation.

Rhabdomyosarcomas generally respond well to chemotherapy, and the residual lesions often are better differentiated than their primaries. This phenomenon may be explained by selective multidrug resistance (MDR) of differentiated tumor cell populations. We assess the role of MDR proteins in chemotherapy-induced differentiation in rhabdomyosarcomas in a clinical setting. Paraffin-embedded samples of 13 pairs of primary untreated rhabdomyosarcomas and their residual, recurrent, or metastatic lesions after chemotherapy were assessed for expression of MDR proteins, including P-glycoprotein (Pgp), multidrug resistance-associated protein (MRP-1), and lung resistance-related protein (LRP). Expression was semiquantitatively scored based on the percentage of isolated immunoreactive tumor cells as follows: 0, negative; 0.5, <5%; 1, 5% to 25%; 2, 26% to 50%; 3, 51% to 75%, and 4, >75%. All specimens after chemotherapy, except the late recurrences, were better differentiated than their primary, untreated specimens. Pgp or MRP-1 expression did not change significantly, but LRP expression increased significantly after chemotherapy. In both untreated and treated samples, LRP was expressed primarily in differentiated cells. The findings indicate that the in vivo expression of LRP, but not of Pgp and MRP-1, is induced by chemotherapeutic treatment in rhabdomyosarcomas. The preferential expression of LRP in differentiated cells and the subsequent more extensive expression after chemotherapy suggests that LRP plays a role in therapy-induced differentiation.

ATP Binding Cassette Transporter, Subfamily B, Mem↗