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H J Hoekstra

Publications and source records attributed to H J Hoekstra.

At least 73 records · Page 4Linked to original sources
PubMed2000

Routine bone scintigraphy in primary staging of soft tissue sarcoma; Is it worthwhile?

BACKGROUND: The incidence of bone metastases in soft tissue sarcoma (STS) patients seems to be low but has not been studied separately. In this study, the authors aimed to determine the value of routine radionuclide bone scanning in preoperative staging of STS patients. METHODS: Preoperative bone scans were evaluated retrospectively in 109 consecutive patients (median age, 44 years; range, 1-86) with intermediate or high grade STS. Scans were scored in 3 categories: 1, metastases very likely; 2, equivocal; and 3, normal or benign lesions. RESULTS: Category 1 scans were found in 8 of 109 patients (7%); in all 8 patients, bone metastases were confirmed. Six of these eight patients reported pain, and all had additional lung, bone marrow, or lymph node metastases. The highest rate (17%) was found in the rhabdomyosarcoma subgroup (n = 18). Category 2 (equivocal) scans were present in 12 of 109 patients (11%), in all of which bone metastases were excluded through additional investigations. Category 3 (normal) scans were found in 81%. Bone metastases were at least as frequent as lung metastases (4%) and were the single site of systemic disease in 4%. The rate of bone metastases was 55% in patients with bone pain versus 2% in patients without pain. CONCLUSIONS: Bone metastases in primary STS patients are rare (7%) yet in this study at least as frequent as lung metastases. The low rate in asymptomatic patients versus the high rate in symptomatic patients supports the use of bone scanning in symptomatic patients only. The yield of routine bone scanning is low.

Adolescent↗
PubMed2000

Frozen section analysis of sentinel lymph nodes in melanoma patients.

BACKGROUND: The sentinel lymph node biopsy (SLNB) is a diagnostic or staging option in the treatment of patients with cutaneous malignant melanoma (CMM) and is investigated intensively. A positive SLNB has appeared to identify patients who might have benefited from a lymph node dissection (LND). Intraoperative frozen section analysis (FSA) of the sentinel lymph node (SLN) during surgery would allow SLNB and LND to be performed in the same procedure. In the current study, we tested the reliability of FSA on the sentinel lymph node in patients with CMM. METHODS: Before definitive treatment of their melanomas began, FSA was performed on the SLNBs of 58 patients, whose median age was 56 (22-81) years, and who were 55% male and 45% female. Serial sections (500 micrometer interval), stained with routine hematoxylin and eosin and immunohistochemistry (S-100 and HMB-45), obtained definitive histology of the sentinel lymph node. RESULTS: Detection of the sentinel lymph node was possible in 56 patients (97%). Sixty-one SLNBs were performed in these patients. FSA detected metastases in 5 of 108 SLN (5%) in 5 patients. This was upgraded after definitive histology to 13 SLN (12%) in 11 patients (20%). Sensitivity of the FSA was 38%. After a median follow-up of 35 (range: 24-54) months, the false-negative rate of the SLN was 4% (2 patients). CONCLUSION: The combination of the low sensitivity of FSA and a finding that only 12% of the SLNBs contained metastases does not justify routine use of FSA on the SLN of patients with CMM.

Adult↗
PubMed2000

Soft tissue leiomyosarcomas and malignant gastrointestinal stromal tumors: differences in clinical outcome and expression of multidrug resistance proteins.

PURPOSE: Several studies have reported clinical behavior and chemotherapy resistance in leiomyosarcomas, but these studies did not differentiate between soft tissue leiomyosarcomas (LMS) and malignant gastrointestinal stromal tumors (GIST). Multidrug resistance (MDR) has been associated with the expression of P-glycoprotein (P-gp), multidrug resistance protein (MRP(1)), and lung resistance protein (LRP). The aim of the present study was to compare LMS and GIST with respect to clinical outcome and MDR parameters. PATIENTS AND METHODS: Clinical outcome was evaluated in 29 patients with a primary deep-seated LMS and 26 patients with a primary malignant GIST. Paraffin-embedded material, available for 26 patients with LMS and 25 with GIST, was used for immunohistochemical detection of P-gp, MRP(1), LRP, and c-kit. RESULTS: Mean overall survival (OS) was 72 months for LMS patients and 31 months for GIST patients (P: <.05). Metastases occurred in 16 (59%) of 27 assessable LMS patients and in 10 (56%) of 18 assessable GIST patients. LMS predominantly metastasized to the lungs (14 of 16 patients), whereas GIST tended to spread to the liver (five of 10 patients) and the abdominal cavity (three of 10 patients; P: <.001). P-gp and MRP(1) expression was more pronounced in GIST than in LMS (P: <.05): the mean percentage of P-gp expressing cells was 13.4% in patients with LMS and 38.4% in patients with GIST, and the mean percentage MRP(1) expressing cells was 13.3% in patients with LMS and 35.4% in patients with GIST. LRP expression did not differ between LMS and GIST. c-kit was expressed in 5% of the LMS patients and in 68% of the GIST patients. CONCLUSION: LMS patients have a better survival than GIST patients, and the metastatic pattern is different. Expression of MDR proteins in LMS is less pronounced than in GIST.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2000

[Poor prognosis of osteosarcoma of pelvis; 39 years of registration by the Netherlands Commission on Bone Tumors].

OBJECTIVE: To evaluate the results of treatment in patients with osteosarcoma of the pelvis. DESIGN: Retrospective. PATIENTS AND METHODS: Sixty-five patients with pelvic osteosarcoma registered in the files of the Netherlands Committee on Bone Tumours over 1957-1995 were reviewed. Complete information was obtained on 62 cases: 27 males and 35 females, median age was 31 years (range: 12-83). Distant metastases were present in 11 patients (stage IIIB; 18%), while 50 patients had stage IIB osteosarcoma (81%) and 1 patient stage IB osteosarcoma (2%). The results of treatment and survival were determined. RESULTS: Median survival was 14 months (2-177), the 5-year survival 15%. Distant metastases developed in 27 of 42 (64%) patients with curatively treated stage IIB osteosarcoma, with prolonged metastasis-free survival after chemotherapy treatment (p < 0.0012). Survival in patients with stage IIB pelvic osteosarcoma was better after surgical resection of the primary tumour than after no operation (p < 0.0054); (neo)adjuvant chemotherapy gave no longer survival than surgery alone (p < 0.083). CONCLUSION: The prognosis of pelvic osteosarcoma was poor, despite modern multimodality treatment regimens, including surgical resection and chemotherapy.

Adolescent↗
PubMed2000

Clinico-pathological data and prognostic factors in completely resected AJCC stage I-III liposarcomas.

BACKGROUND: In general, although biological behavior and prognosis of liposarcomas (LPS) are more favorable compared with most other soft tissue sarcomas (STS), prognosis can vary widely depending on tumor characteristics, especially histological subtype and tumor grade. PATIENTS AND METHODS: All consecutive, completely resected stage I-III LPS (as determined by the American Joint Committee on Cancer staging guidelines), treated at the Groningen University Hospital from 1977-2000, were analyzed. RESULTS: A total of 69 patients, 35 males and 34 females, median age 51 (range 11-80) years, were reviewed. After a median follow-up of 71 (range 5-231) months, the overall local recurrence and metastasis rate at five years after diagnosis were 27% and 16%, respectively. Retroperitoneal localization was a significant negative prognostic factor regarding local recurrence; dedifferentiation, grade II-III, and deep location regarding distant metastasis; and dedifferentiation, grade II-III, stage II-III, size >20 cm and non-radical resection regarding survival. CONCLUSIONS: LPS have a relatively mild biologic behavior, with the exception of very large, deeply located, dedifferentiated and/or grade II-III LPS. Radical resection is important for disease-specific survival. LPS have a relatively mild biologic behavior, with the exception of very large, deeply located, dedifferentiated and/or grade II-III LPS.

Adolescent↗
PubMed2000

Effect of single chemotherapeutic agents on the growing skeleton of the rat.

BACKGROUND: To establish the effect of chemotherapeutics on the growing skeleton, male Wistar rats were studied. DESIGN: Between the ages of 4 and 13 weeks the rats were given i.v. doxorubicin 15 mg/m2 body surface area (BSA), methotrexate 60 mg/m2 BSA or cisplatin 7.5 mg/m2 BSA. For each group of drug-treated rats there was a diet-matched control group that was injected with a placebo only. Rats fed ad libitum served as the basic control group for length and weight growth. Body weight and tibial length were measured weekly. Kidney and liver weight were determined at the end of the study. RESULTS: Weight gain and length growth were significantly decreased in the diet controlled groups (P < 0.05). Doxorubicin reduced length growth with 4.12 mm or 18% (P < 0.05). Methotrexate reduced length growth with 1.11 mm or 5% (P < 0.05). Length growth in the cisplatin treated rats did not differ from the diet controls. CONCLUSIONS: Doxorubicin and methotrexate decrease length growth in the rat tibia by, respectively, 18% and 5%. Cisplatin does not affect length growth. The decrease in growth might be a direct effect of doxorubicin and methotrexate on the tibial growth plate and metaphysis, but may be more pronounced due to the malnutrition.

Animals↗
PubMed2000

The 16p11 breakpoint in myxoid liposarcomas might affect the expression of the LRP gene on 16p11.2 encoding the multidrug resistance associated major vault protein.

BACKGROUND: Chromosome breakage could influence the expression of genes. This has been noticed in specific cases of acute myeloid leukaemia, where the 16p13 breakpoint affects the expression of the multidrug resistance related protein (MRP). Myxoid liposarcomas (LPS) are characterized by the t(12; 16)(q13; p11), which leads to the formation of a FUS-CHOP fusion transcript. This study investigates the relationship between the cytogenetically detected breakpoint 16p11 in myxoid LPS, the presence of the FUS-CHOP fusion transcript in nonmyxoid LPS and the expression of the lung resistance major vault protein (LRP) gene on 16p11.2. MATERIALS AND METHODS: Of 16 cases with a diagnosis of a (possible) liposarcoma with an abnormal karyotype, fresh frozen tumour material was available for immunohistological detection of LRP. Cases without a cytogenetically detected t(12; 16)(q13; p11), were analyzed for the presence of a FUS-CHOP fusion transcript by RT-PCR. RESULTS: In all 9 myxoid LPS a t(12; 16)(q13; p11) was found and LRP expression was absent or low. In none of the remaining 7 cases was a FUS-CHOP fusion transcript found, and four tumours were LRP positive (P = 0. 02). LRP expression in myxoid LPS (mean: 1.3%) was lower (P = 0.07) than in the nonmyxoid tumours (mean: 35.7%). CONCLUSIONS: These observations indicate a relation between the t(12; 16)(q13; p11), leading to a FUS-CHOP fusion transcript in myxoid LPS, and the low or absent expression of the LRP-gene located on 16p11.2.

Chromosome Aberrations↗
PubMed2000

The effect of chemotherapy on the growing skeleton.

With the increasing use of high dose (poly)chemotherapy schedules in the treatment of childhood cancer it is particularly important to know the adverse effects of these treatments. Growth is a complex mechanism affected not only by chemotherapy but also by the malignancy itself as well as nutritional status, the use of corticosteroids and (cranial) radiation. In vitro and animal studies are often the most useful in determining the effect of a single chemotherapeutic agent on the growing skeleton. In vitro studies have shown doxorubicin, actinomycin D and cisplatin to have a direct effect on growth plate chondrocytes that in animals results in decreased growth and final height. Clinical studies with multiagent chemotherapy have demonstrated that antimetabolites decrease bone growth and final height. Childhood cancer survivors are at risk of a reduced bone mineral density, mainly due to methotrexate, ifosfamide and corticosteroids. This reduced bone mineral density persists into adult life and may increase bone fracture risk at an older age.

Adult↗
PubMed2000

Osteosarcoma of the pelvis--oncological results of 40 patients registered by The Netherlands Committee on Bone Tumours.

AIM AND METHODS: We reviewed the oncological outcome in 40 consecutive patients with an osteosarcoma of the pelvic region, registered in the files of the Netherlands Committee on Bone Tumours (NCBT) between 1978 and 1995. RESULTS: Six patients had distant metastases at initial presentation (Enneking stage IIIB), 33 patients had stage IIB osteosarcoma and one patient stage IB osteosarcoma. Patients with metastases were treated with chemotherapy (four) or palliative procedures (two). Patients with non-metastatic osteosarcoma were treated with surgical procedures with (14) or without (four) neoadjuvant chemotherapy, chemotherapy without surgical resection (nine), or palliative procedures (seven). The median survival of stage IIB and IIIB osteosarcoma was 14 months (2-175) and 7.5 months (2-16), respectively. Survival in patients with stage IIB osteosarcoma treated with curative procedures was significantly better (P<0.0006) compared with stage IIB patients treated with palliative intent. Two and 5-year survival for patients with curatively treated stage IIB osteosarcoma was 35% and 26%, respectively; distant metastases had developed in 65% of these patients. On univariate analysis, positive prognostic factors for patients with stage IIB osteosarcoma were complaints of 3 months or less before initial presentation, tumour size of 8 cm or less, osteoblastic subtype, surgical resection of the primary tumour and limb salvage procedures. CONCLUSION: In conclusion, the prognosis of pelvic osteosarcoma remained poor despite modern multimodality treatment regimens, including neoadjuvant chemotherapy.

Adolescent↗
PubMed2000

Educational tips in the treatment of malignant ulcerating tumours of the skin.

Coping with ulcerating or bleeding tumours or metastases of the skin that are not suitable for curative or palliative treatment poses a problem for patients, doctors and nursing staff. Treatment should focus on limiting local and systemic infection, combating unpleasant odours and reducing bleeding. Palliative amputation is sometimes a reasonable option. Treatment depends on the nature and site of the tumour and should be tailored to and carried out in consultation with the patient, the treating specialist and the oncology nursing team. The goal of treatment is to optimize the quality of life of patients in the terminal phase.

Arm↗
PubMed2000

Hyperthermic isolated regional perfusion of the limb with carboplatin.

AIMS: To investigate the feasibility of hyperthermic isolated regional perfusion (HIRP) with carboplatin in the management of locally recurrent and/or intransit metastases of melanoma or locally advanced soft tissue sarcoma. METHODS: Three patients, two with locally advanced melanoma and one with a low-grade liposarcoma of the lower extremity, were treated with HIRP under mild hyperthermia (39-40 degrees C) with 125 mg carboplatin/l perfused limb volume. RESULTS: No systemic toxicity was observed. Local toxicity consisted of post-perfusion oedema present in all three patients which resolved within 2 weeks. Clinically, a persistent local neuropathy was observed in all three patients, two of which were confirmed by electromyogram and nerve conduction study. Severe motor-sensory neuropathy was located mainly in the peroneal and sural nerves of the perfused limbs. Pharmacokinetic parameters of the carboplatin showed a higher concentration of carboplatin in the skin compared to the muscle. The two melanoma patients showed a complete response but developed local recurrences within 1.5 years after perfusion. The third patient underwent a delayed excision of the sarcoma 8 weeks after perfusion which revealed 50% viable tumour. One of the melanoma patients and the sarcoma patient died from lung metastases 56 and 31 months post-perfusion treatment, respectively. The other melanoma patient is alive 95+ months post-perfusion treatment. CONCLUSIONS: The local neurotoxicity observed did not warrant further research of carboplatin in HIRP.

Aged↗
PubMed2000

Procalcitonin behaves as a fast responding acute phase protein in vivo and in vitro.

OBJECTIVES: Procalcitonin (PCT) is a 13 kD protein of which plasma concentrations are strongly increased in inflammatory states. PCT concentrations are claimed to have a more powerful discriminatory value for bacterial infection than the acute phase proteins serum amyloid A (SAA) or C-reactive protein (CRP). The source of production and its mechanism of induction are unknown. We investigated the inducibility of PCT both in vivo and in vitro and compared the behavior of PCT with those of SAA and CRP. DESIGN: A prospective descriptive patient sample study and a controlled liver tissue culture study. SETTING: A university hospital. PATIENTS: Cancer patients who were treated with human tumor necrosis factor-alpha (rhTNF-alpha; 5 patients) or interleukin-6 (rhIL-6; 7 patients). MEASUREMENTS AND MAIN RESULTS: Serial serum samples were collected for analysis of concentrations of PCT, SAA, and CRP. In the TNF-alpha group, frequent sampling was performed on the first day to allow analysis of initial responses. In a human liver slice model, the release of PCT, SAA, and CRP was measured on induction with rhTNF-alpha and rhIL-6 for 24 hrs. We found that PCT displayed acute phase reactant behavior in vivo after administration of both rhTNF-alpha and rhIL-6. After rhTNF-alpha-administration, PCT reached half-maximal concentrations within 8 hrs, 12 hrs earlier than either SAA or CRP did. PCT, SAA, and CRP were produced in detectable quantities by liver tissue in vitro. PCT production by liver slices was enhanced after stimulation with rhTNF-alpha or rhIL-6; SAA and CRP concentrations were elevated after stimulation with rhTNF-alpha. CONCLUSIONS: We found that PCT and acute phase proteins such as CRP are induced by similar pathways. The liver appears to be a major source of PCT production. Thus, PCT may be considered an acute phase protein. The different kinetics of PCT, rather than a fundamentally different afferent pathway, may explain its putative diagnostic potential to discriminate bacterial infection from other causes of inflammation.

Bacterial Infections↗
PubMed2000

Tissue damage after single high-dose intraoperative irradiation of the canine liver: evaluation in time by means of radionuclide imaging and light microscopy.

To establish the tolerance of liver tissue to single high-dose intraoperative irradiation, the histopathological changes in the canine liver after single high-dose intraoperative irradiation were investigated by means of radionuclide imaging and light microscopy. Intraoperative irradiation at doses of 0, 10, 20, 25 or 30 Gy was applied to a part of the liver of 25 beagles. Radionuclide imaging using (99m)Tc-sulfur colloid was performed at several times during follow-up. Elective humane killing was done 3 months and 1, 2, 3 and 5 years after irradiation. Light microscopy was used to identify histopathological alterations. There was no morbidity or mortality during a maximal follow-up of 5 years. In 40% of the animals, a region of diminished uptake was observed at the irradiation site. The regions of diminished uptake of the radiopharmaceutical agent became smaller with time. Light microscopic examination revealed severe parenchymal fibrosis, liver cell atrophy, and bile duct proliferation at the irradiated area 1 to 2 years after irradiation. At 3 and 5 years, vascular changes with endothelial proliferation and focal arteriolar hyalinosis were observed. This study demonstrates that intraoperative irradiation of a part of the liver in the canine model can be applied safely. Light microscopy confirmed that histological damage was not always accompanied by diminished uptake of the radiopharmaceutical agent at the irradiation site.

Animals↗
PubMed2000

Imaging of soft-tissue tumors using L-3-[iodine-123]iodo-alpha-methyl-tyrosine single photon emission computed tomography: comparison with proliferative and mitotic activity, cellularity, and vascularity.

The radiolabeled amino acid L-3-[123I]-iodo-alpha-methyltyrosine (IMT) is a new tumor tracer that accumulates in many tumors and is suitable for single photon emission computed tomography (SPECT) imaging. Using IMT SPECT, we studied 32 patients with a soft-tissue tumor suspected to be a soft-tissue sarcoma to determine whether: (a) tumors can be visualized; (b) benign and malignant lesions can be distinguished; and (c) IMT uptake is related to tumor grade and proliferation. Whole-body imaging was performed 15 min after administration of 300 MBq IMT, biopsy, or resection 1-2 weeks later. IMT uptake was quantified using a region-of-interest method resulting in tumor:background (T:B) ratios. These were compared with tumor grade, mitotic index, tumor cellularity, vascularity, and the Ki-67 proliferation index. Eleven patients had a benign tumor, and 21 patients had a soft-tissue sarcoma. Six benign tumors demonstrated minor IMT uptake, and five lipomas had no uptake. All malignant tumors had high uptake and were clearly visualized. T:B ratios in malignant tumors (3.83 +/- 1.16) were higher (P < 0.001) than in benign tumors (1.52 +/- 0.60). Small (<5 mm) metastases in two patients were not detected. Taking the T:B ratio 2.0 as the cutoff level, the sensitivity for detection of malignancy was 100%, and specificity was 88%. IMT uptake correlated with histological grade (r = 0.82; P < 0.001), mitotic index (r = 0.75; P < 0.001), tumor cellularity (r = 0.73; P < 0.01), and with the Ki-67 proliferation index (r = 0.63; P < 0.01). In conclusion, IMT SPECT visualized all soft-tissue sarcomas. Uptake in sarcomas was clearly higher than in benign lesions, yielding 100% sensitivity for detection of malignancy at 88% specificity. Uptake increased with higher tumor grade and higher proliferation rate.

Adolescent↗