Biomedical subjects
Publications and source records attributed to A Van Oosterom.
A first course of combination chemotherapy for large volume metastatic disease in a patient with Merkel cell carcinoma resulted in a tumor lysis syndrome. After this course a nearly complete response was documented. This case report extends further the chemosensitivity of Merkel cell carcinoma and demonstrates the need for tumor lysis syndrome prophylaxis in patients with bulky disease or fast-growing tumors.
A volume conductor model is presented in which the aspects of finite volume conductor dimensions and finite muscle fiber length are combined. The effects of these aspects on single muscle fiber action potentials (SFAPs) and on motor unit action potentials (MUAPs) are shown and verified with surface recorded motor unit action potentials. It is demonstrated that the influence of the fiber length being finite is enhanced significantly by the finite limb dimensions of the volume conductor model, for single fiber action potentials as well as for motor unit action potentials. The model described is found to be capable of generating surface MUAPs which show a very good resemblance with measured surface MUAPs. Recorded MUAPs illustrate clearly the effects caused by finite muscle fiber length. The effect of finite limb dimensions in simulated intramuscular MUAPs was evidently less dominant than in simulated surface MUAPs.
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In multicentre studies, non-compliance with the protocol may limit the chances of reaching a correct conclusion. A procedure to examine the administration of chemotherapy in multicentre EORTC protocols has been developed. General aspects are covered in a mailed questionnaire on the prescription of drugs with rounding up or down of dosages, local facilities for preparation and the procedure for preparation and administration. More detail is collected during a quality control site visit. Ten centres have been visited and there was significant variation between centres in the organisation of chemotherapy administration. However, more striking differences were noted between the type and quality of hospital files. The lack of systematic recording of sequence, timing and doses of chemotherapy and, in particular, treatment related toxicity, is a major difficulty limiting the effectiveness of quality control. These shortcomings emphasise the need for standardisation of some aspects of case records and a suggested check-list has been drafted.
Two patients are reported in whom an initial diagnosis of disseminated non small cell bronchogenic carcinoma was subsequently changed into a final diagnosis of extragonadal germ cell tumour. The clinical importance of the differential diagnosis between these two malignancies is highlighted and the management of extragonadal germ cell tumours is discussed.
Extracellular potential waveforms resulting from the termination of the propagation of the transmembrane potential at the end of an active muscle fiber are studied. The transmembrane potential along the muscle fiber is calculated from Hodgkin-Huxley-like equations with axially varying parameters under the condition of increasing axial resistance, decreasing ionic conductances, or decreasing radius at the muscle fiber end. The extracellular potential distribution is calculated using the derived transmembrane current as a line source in an unbounded volume conductor. Potential waveforms with constant latency at extracellular points far from the fiber end are presented and are compared with measurements and simulations from literature. Monophasic waveforms with constant latency are found. The polarity and the amplitude as a function of axial and radial position relative to the fiber end indicate that an equivalent dipole source adequately represents the propagation stop at the fiber end. An expression for the dipole moment in terms of fiber radius, intracellular conductivity, and transmembrane potential is derived.
In the classical core conductor model the intra- and extracellular media of an infinitely long nerve or muscle fiber in a volume conductor are represented by parallel axial resistances. Thus, volume conductor properties are neglected. In this paper a study is presented that relates the conductivity of the intra- or extracellular medium of the fiber to the axial resistance used in the core conductor model. Expressions for the axial resistances that are dependent on the spatial frequency of the membrane current source density are derived from a volume conductor approach.
Despite the low incidence of sarcomas, the Soft Tissue and Bone Sarcoma Group has established itself as one of the more active cooperative groups of the European Organization for Research and Treatment of Cancer. Performing over a 10 yr period three phase III protocols (total entry 750 patients), three randomized phase II studies (464 patients), a pilot combination study (185 patients), and 12 phase II studies (406 patients). The new randomized phase III protocol for advanced soft-tissue sarcoma will provide an interesting test of the validity of the current membership policy, which has not discouraged the participation of enthusiastic new members. For extremity sarcomas, improved surgical techniques have increased the number of patients retaining functional limbs but have maintained excellent rates of local control. However, systemic metastasis remains a significant problem and presents a challenge for future adjuvant studies.
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An interim analysis of the current EORTC studies in advanced testicular cancer indicates that (a) for low volume metastatic disease the addition of bleomycin (B) to etoposide (E) and cisplatinum (P) may not be necessary, and (b) for high volume metastatic disease the alternating schedule of PVB/BEP is not superior to treatment with BEP. Future studies will subdivide patients into 3 groups. Those with low volume metastatic disease will receive EP using 2 dose schedules for cisplatin. Those with high volume metastases will receive either BEP or etoposide, ifosfamide and cisplatinum (VIP). Those with ultra-high volume metastases will receive BOP/VIP, possibly randomised against another intensive chemotherapy schedule.
The appearance of metastatic disease heralds disaster for the vast majority of patients with renal carcinoma. A few spontaneous regressions of established metastases have been reported but no systemic chemotherapeutic treatment withstood the test of time or critical analysis. This analysis requires objective remissions in measurable metastatic disease evaluated against well-defined prognostic factors in relation to survival with quality of life for the patient. No single agent chemotherapy achieved a desired 20% response rate and only a few combination studies, especially with immunotherapy, reported significant clinical results. We recommend that the variable biological potential of renal metastatic disease be harnessed in prospective multicentric phase I/II trials with strict response and prognostic criteria to search for new antineoplastic agents for this disease.
This study validates current hypotheses for the generation of so-called far-field or stationary somatosensory evoked potential (SEP) components. Changes in the volume conductor configuration and changes in the direction of nerve propagation are demonstrated to be capable of generating such components. Results are based on basic aspects of the theory of volume conduction. It is shown that in an essentially restricted volume conductor any disturbance of uniform nerve propagation in a homogeneous extracellular medium will lead to the generation of non-moving field components. A number of illustrative examples are presented in which intermingling of non-moving and propagating potential fields can be observed. These results can be helpful in unravelling complicated wave forms from the nervous system in which both types of potential field can be distinguished. It is shown that realistic changes within the volume conductor can lead to substantial far-field components. This type of volume conductor induced 'virtual generators' or 'secondary sources' is present in the peripheral nervous system and most probably also in the inhomogeneous structures of the brain.
One hundred and seventy-one patients with advanced soft tissue sarcoma entered a randomized crossover phase II study comparing cyclophosphamide (CYCLO) with a new analogue, ifosfamide (IFOS), both administered as 24 h i.v. infusions every 3 weeks. The doses used were CYCLO 1.5 g/m2 and IFOS 5 g/m2, with provision for dose escalation. All patients received mesna 400 mg/m2 as an i.v. bolus 4 hourly X 9 doses, commencing at the start of the oxazophosphorine infusion. Patients who had received previous chemotherapy were eligible provided this did not include a classical alkylating agent. There were 22 patients who were ineligible, and response could not be evaluated in 12 additional patients. IFOS produced two complete and ten partial remissions, for an overall response rate of 18%. CYCLO was significantly (P = 0.04) less active, producing one complete and five partial remissions, an overall response rate of 9%. Stabilization of disease was similar in both arms (27% and 24% respectively), but fewer patients showed progression on IFOS. The response rate was higher (20% vs 5%) for patients who had not received previous chemotherapy, and also for female compared with male patients (21% vs 5%). When only patients who had not received previous chemotherapy were considered, the respective response rates for IFOS and CYCLO were 24% and 15%. There were no responses in previously treated patients receiving CYCLO. There were four partial responses in 33 patients crossing from CYCLO to IFOS, but no responses in 18 patients receiving CYCLO after IFOS. Leucopenia was significantly more pronounced (P = 0.0004) with CYCLO, both after the first course and throughout treatment, although the incidence of severe infections, 6%, was the same in both arms. Nausea and vomiting were more severe with IFOS (P = 0.022), but other toxicities were mild. Grade 1 or 2 bladder (haematuria) or renal (rise in serum creatinine) toxicity was slightly more frequent with IFOS (7 vs 3 patients) and was a reason for stopping treatment for one patient in each arm. Three episodes of mild to moderate drowsiness after IFOS were reported, but no severe encephalopathy. A higher response rate with less myelosuppression suggests that IFOS may have advantages over CYCLO in combination with such active agents as adriamycin.
Twenty-nine evaluable patients with extensively pretreated breast cancer received PALA, a new pyrimidine antimetabolite. The drug was given by intravenous infusion over 60 min, at a daily dose of 2.5 g/m2 for 2 consecutive days. Courses were repeated at 2-week intervals and doses were escalated to toxicity. Two objective partial remissions were observed, lasting for 3 and 4.5 months respectively. Toxic effects were dose-related and consisted mainly of mucocutaneous manifestations, i.e., skin rashes, stomatitis, diarrhea, conjunctivitis and corneal ulcerations. Evidence of antitumor potential in far-advanced disease and lack of myelosuppression point to the need for additional trials of PALA in a more favorable selection of patients with breast cancer.
Thirty-six patients with measurable or evaluable advanced soft tissue sarcoma were entered in a phase II trial with PALA. Among the 27 evaluable patients, 15 were men, the median age was 55 yr (16-69) and the median performance status (Karnofsky) was 80 (50-100). Most patients had leiomyosarcoma (8), liposarcoma (3), neurofibrosarcoma (3), synovial cell sarcoma (3), or undifferentiated sarcoma (3). Indicator lesions consisted essentially of lung metastases (21) and/or soft tissue lesions (14). All patients had received prior chemotherapy with 1-5 regimens and 6 had achieved objective response with these previous treatments. PALA was given as a 60-min i.v. infusion at a daily dose of 2.5 g/m2 for two consecutive days. Courses were repeated every two weeks. A median number of 3 courses (2-17) were administered. Partial remission (greater than 50%) was obtained in one patient with a liposarcoma who had also responded to prior combination chemotherapy. This single response to PALA lasted 6 weeks from initiation of therapy. Four patients had unchanged disease after 6+ courses of PALA and 22 had progressive disease. Toxic effects were generally mild to moderate and included cutaneous toxicity (17), diarrhea (14), stomatitis (13), ocular manifestations, consisting of conjunctivitis, corneal ulceration and/or photophobia (11), nausea and vomiting (6) and, possibly, seizures (2). There was no evidence of drug-related myelosuppression. It is concluded that PALA given at the dose schedule selected for this trial has no significant antitumor activity in advanced soft tissue sarcoma previously treated with chemotherapy.
OBJECTIVE: To assess the results of retroperitoneal lymph node dissection (RPLND) of residual masses in patients with disseminated non-seminomatous germ cell tumour treated with cisplatin-based chemotherapy, both in terms of extension of surgery, morbidity and survival. PATIENTS AND METHODS: Retrospectively, all patients treated for non-seminomatous germ cell tumour at the University Hospital of Antwerp were studied from January 1987 till December 1997. In patients with non-seminomatous testicular cancer more than stage I, the 'wait and see' strategy changed and patients were treated with chemotherapy. Patients were assessed at the end of chemotherapy and if a residual masses persisted, a RPLND was performed. If possible, a nerve-sparing lymphadenectomy was performed. Extension of surgery, morbidity and survival were analysed. RESULTS: Sixty patients had a non-seminomatous germ cell tumor of the testis and were analysed. The median follow-up was 78 months (range: 13-144 months). Thirteen patients with stage I disease were treated with orchiectomy only and none of these patients had recurrent disease. Forty-seven patients were treated with cisplatin-based chemotherapy. A complete response was observed in sixteen patients (34%), while 31 patients (66%) achieved a partial response and were treated with a RPLND. Fifteen patients underwent RPLND above the level of the renal trunk. In two patients malignant cells or fibrotic tissue were found above the renal trunk and bilateral. In five patients viable tumour cells were found in the region below the renal trunk. Sixteen patients underwent RPLND below the level of the renal trunk, of which nine had a unilateral resection, containing viable tumour in two patients. Operative mortality was 0%. One patient died six months after RPLND due to metastatic disease. In two patients, an important retroperitoneal bleeding occurred. Resection of adherent organs was performed in two patients. Long term sexual problems were reported by thirteen patients (65%) with bilateral lymphadenectomy versus two patients (18%) in the unilateral group. The survival of the patients treated with a RPLND was 97% and in the whole group of patients with a non-seminomatous testicular cancer 98%. CONCLUSION: RPLND has a place in the treatment of patients with non-seminomatous testicular cancer after chemotherapy in case of residual masses. Although mortality is low, morbidity is acceptable. In a limited number of patients there was a need of resection of adherent organs when a resection above the renal trunk was performed.
Gastrointestinal stromal tumours (GIST), previously classified as smooth muscle tumours, are the most common mesenchymal tumours of the digestive tract. Since the discovery of KIT (CD 117) expression, these tumours can be diagnosed confidently by pathology. Until recently, surgery was the only treatment available because these tumours were not sensitive to chemotherapy nor radiation therapy. In the long run most of these tumours recurred in the abdominal cavity or in the liver. Recently a new drug STI 573 (Glivec) showed very promising results in metastatic disease with response rates of about 65%. In six patients treated at our center, surgery was indicated during STI therapy because of subobstruction, skin necrosis, abdominal distention, bleeding. Surgery proved to be safe and efficient, allowing continuation of STI therapy in much better circumstances.
BACKGROUND: The study aimed at evaluating the potential benefit from a combination of fractionated ionising radiation with the vascular-targeting compound combretastatin A-4 phosphate (CA-4-P). MATERIALS AND METHODS: Syngenic rat rhabdomyosarcoma (R1), growing subcutaneously, was treated at 2 different sizes: either small (2 +/- 0.5 cm3) or large (10.94 +/- 0.6 cm3). Localised fractionated irradiation of the tumours (5 x 3 Gy) in 5 days was followed 1 day later by an intraperitoneal CA-4-P treatment (25 mglkg). RESULTS: The combined treatment of only large tumours resulted in a small additional growth delay when compared with radiotherapy only. CONCLUSION: The present data indicate a size-dependent increase in tumour growth delay from combining fractionated irradiation with CA-4-P.