Re: Axillary lymph node staging in breast cancer by 2-fluoro-2-deoxy-D-glucose-positron emission tomography: clinical evaluation and alternative management.
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Breast Neoplasms↗
Biomedical subjects
J J van der Hoeven
Publications and source records attributed to J J van der Hoeven.
[Added value of positron emission tomography with fluoro-18-deoxyglucose as the tracer (FDG-PET) in clinical problem cases in oncology].
Positron emission tomography with fluoro-18-deoxyglucose as tracer molecule (FDG-PET) is a relatively new imaging technique used in oncology to study tumour metabolism in vivo. Both qualitative and quantitative data obtained by PET provide unique information to the clinician and may guide the therapeutic approach in selected patients, where conventional diagnostic tests like CT or MRI yield equivocal results. According to the experience obtained in the Vrije Universiteit Medical Centre in Amsterdam, the additional value of FDG-PET can be explained by the sensitivity and the specificity of the technique, combined with the visualization of the whole body. FDG-PET may reveal metastases and tumour tissue may be differentiated from scar tissue and necrosis. PET is expensive and its effects on patient outcome has yet to be established.
Adult↗
Controlled multicentre study of the influence of subcutaneous recombinant human erythropoietin on anaemia and transfusion dependency in patients with ovarian carcinoma treated with platinum-based chemotherapy.
This randomised controlled multicentre trial evaluated the effectiveness of recombinant human erythropoietin (rhEPO) in preventing anaemia and reducing the need for blood or erythrocyte transfusion in 122 ovarian cancer patients receiving platinum-based chemotherapy. The patients were randomly allocated to receive rhEPO 150 U/kg or 300 U/kg subcutaneously, three times a week, or open control. Patients also received up to 6 cycles of carboplatin or cisplatin, alone or in combination with other cytotoxic agents. Intention-to-treat analysis showed that 39.4% of patients in the control group received at least one blood transfusion, compared with 9.2% of patients treated with rhEPO. Patients treated with rhEPO experienced a significantly longer time to first erythrocyte transfusion than the control group and were less likely to experience nadir haemoglobin levels < 10 g/dl (P < 0.001 and < 0.05, respectively). A haemoglobin decrease < 1 g/dl during the first chemotherapy cycle, as well as a low baseline serum erythropoietin concentration, predicted a low transfusion need in rhEPO-treated patients but not in controls. During the study, 103 patients suffered at least one adverse event, but no serious, and only nine non-serious adverse events were considered possibly related to rhEPO therapy. These results indicate that treatment with rhEPO prevents anaemia, it reduces the need for blood or rhEPO erythrocyte transfusion in patients with ovarian cancer receiving platinum-based chemotherapy, and it is well tolerated. A starting dose of 150 U/kg of rhEPO, three times a week, may be recommended.
Anemia↗
Spontaneous fracture of implanted central venous catheters in cancer patients: report of two cases and retrospective analysis of the 'pinch-off sign' as a risk factor.
Spontaneous fracture of central venous catheters (CVC) has been reported. It results from repeated compression of the extravasal part of the CVC between the clavicle and the first rib. The so called pinch-off sign (POS) of the CVC as visible on a chest radiograph has been described as a warning for this complication. Fracture of CVC in patients receiving chemotherapy results in extravasation of the drug which may have serious consequences. We describe the spontaneous fracture of a CVC in two cancer patients. Subsequently we retrospectively analyzed chest radiographs for the POS of 77 cancer patients who received chemotherapy through a CVC and correlated these results with the occurence of complications related to CVC compression. In 77 patients a total of 97 CVC were implanted for a median duration of 7 months. Four CVC (4%) showed a grade 2 POS (change in course of CVC)CVC with luminal narrowing) on a chest radiograph. In three of these (75%) a compression-related complication occurred versus no compression-related complications in 93 CVC showing a POS of grade 1 (change in course of CVC without narrowing) or 0 (no change in course of CVC). The grade of POS on a chest radiograph may vary with the position of the patient, but all grade 2 POS were visible in the upright position. We recommend a chest radiograph in the upright position after placement of a CVC for grading of the POS. CVC showing a grade 2 POS should be removed or at least checked by a chest radiograph before the start of each chemotherapy infusion.(ABSTRACT TRUNCATED AT 250 WORDS)
Adenocarcinoma↗
Bepridil in combination with anthracyclines to reverse anthracycline resistance in cancer patients.
The use of calcium antagonists as multidrug resistance reversing agents is limited by acute cardiac toxicity which, for verapamil, becomes prohibitive when concentrations in plasma approach those required in vitro for its action. A new calcium antagonist, bepridil, is as active as verapamil in reversing drug resistance in vitro. In addition, bepridil has some more favourable pharmacological properties compared with verapamil and other calcium antagonists. 14 patients with progressive advanced cancer, resistant to doxorubicin or epirubicin, were treated with the same anthracycline in combination with bepridil. Bepridil was administered in a continuous 36 h infusion at 22 mg/kg/36 h, with a dose scheme which should result in a steady state plasma concentration of approximately 5 mumol/l, able to reverse anthracycline resistance in vitro. Pharmacokinetic studies demonstrated a median bepridil plasma concentration of 5.3 mumol/l (range 2.6-19.3 mumol/l), at the time of administration of the anthracycline. No acute cardiac toxicity was observed and apparently bepiridil did not induce an increase or change in anthracycline toxicity. However, 2 patients developed overt chronic heart failure after treatment discontinuation, which caused 1 patient's death, and a significant reduction in left ventricular ejection fraction was seen in 4 patients. This chronic cardiac toxicity could be related to the total anthracycline dose received. 5 patients attained short lasting minor responses, 3 had stable disease and 6 progressed. Immunohistochemical studies in 7 tumours failed to reveal P-glycoprotein expression. Further trials with escalating doses of bepridil in combination with multiple drug resistance related anticancer agents are warranted.
Adult↗
Qualitative and quantitative kinetics of submucosally administered antibody fragments in patients with rectal carcinoma: the detection of lymph node metastasis in relation to local tracer diffusion.
Immunoscintigraphy after submucosal administration of a mixture of 131I-anti-CEA and 131I-anti-CA-19-9 around the tumor in patients with rectal carcinoma may improve pre-operative staging and may contribute to the selection of patients eligible for local treatment. However, visual discrimination of local lymph node metastasis appears unreliable, partly because of scatter from the injection site and substantial diffusion of the radiotracer into the interstitium. Analysis of the diffusion profile, however, may improve the sensitivity and accuracy of this immunoscintigraphic approach.
Aged↗
Immunohistochemical detection of P-glycoprotein in human tumor cells with a low degree of drug resistance.
We report the immunohistochemical detection of the 170-180 kDa multi-drug-resistance-related P-glycoprotein in human tumor cells with a low level of resistance. A series of human squamous lung cancer cell lines with increasing levels of resistance to doxorubicin (DOX) was developed and stained for P-glycoprotein, using the JSB-IMAb. Subline SW1573/50A with a 4- to 6-fold cross-resistance to daunorubicin (DNR) and vincristine (VCR) showed rather uniform positive staining for P-glycoprotein apparently at cytoplasmic sites. Only in cells with higher degrees of resistance (greater than 10-fold) could plasma-membrane-associated P-glycoprotein be made visible. DNR efflux was increased in SW1573/50A as compared to the parent line SW1573 (52 and 70% DNR were retained during 3 min efflux respectively). Verapamil partially reversed DNR and VCR resistance in SW1573/50A. Cells obtained from a metastasized renal cell carcinoma and cultured in vitro stained in a similar way to SW1573/50A and showed some sensitivity to verapamil modulation of VCR cytotoxicity. Our results suggest that weakly resistant cancer cells obtained from patients can be routinely detected with JSB-I on cytospins, and implicate that in such weakly resistant cells P-glycoprotein may be present, while plasma membrane expression is not yet readily detectable.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Swelling of metastatic tumors with high-dose interleukin therapy.
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Edema↗
Potentiation of doxorubicin cytotoxicity by the calcium antagonist bepridil in anthracycline-resistant and -sensitive cell lines. A comparison with verapamil.
The ability of the calcium channel blocker bepridil (Bp) to potentiate doxorubicin (Dx) cytotoxicity and enhance its accumulation in anthracycline-sensitive and -resistant human ovarian carcinoma cells (A2780 and 2780AD) and Chinese hamster ovarian (CHO) cells (AUXB1 and CHRC5) was compared with that of verapamil (Vp). A continuous exposure (48-72 h) to Bp as well as Vp potentiated Dx cytotoxicity in 2780AD cells. In short-term incubations (2 h Dx and 4 h calcium channel blocker) the same effects were observed: 4 microM Bp (4Bp) and Vp (4Vp) were equipotent, but at concentrations of 1 and 2 microM, Vp was more active (4Vp = 4Bp greater than 2Vp greater than 2Bp greater than 1Vp greater than 1Bp). In CHRC5 cells the corresponding sequence was: 4Vp greater than 4Bp greater than 2Vp greater than 2Bp greater than 1Vp greater than 1Bp. At high (marginally inhibitory) concentrations, Bp and Vp reversed Dx resistance completely in CHRC5 cells and partly in 2780AD cells. No significant potentiation of Dx cytotoxicity by Bp or Vp was found in A2780 cells, but both were active in AUXB1 cells. In studies with radiolabelled Dx (2 microM), Bp and Vp (16.5 microM) stimulated accumulation in CHRC5 cells almost up to the level in AUXB1 cells. Dx accumulation in 2780AD cells (52 pmol/10(6) cells) could be stimulated to a maximum of about 90 pmol/10(6) cells (drug level in A2780 cells was 153 pmol/10(6) cells). Also, Bp- and Vp-induced stimulation of Dx accumulation was observed in AUXB1, but not in A2780 cells. Bp effected a dose-dependent inhibition of Dx efflux from preloaded 2780AD cells, but not from A2780 cells. We conclude that Bp is more effective than Vp in reversing resistance when both compounds are used in vitro at concentrations which are clinically achievable in plasma.
Bepridil↗
Daunomycin accumulation in resistant tumor cells as a screening model for resistance modifying drugs: role of protein binding.
A potential screening system for drugs that modify anthracycline resistance was investigated. The effect of the calcium antagonistic agents verapamil, diltiazem, bepridil and Ro 11-2933/001 on daunorubicin (DNR) accumulation in the doxorubicin resistant cell line 2780AD was measured. For this purpose cells were suspended in medium with varying concentrations of bovine serum albumin (BSA) and in human plasma to establish the influence of protein binding on DNR accumulation. Increase of protein concentration did not affect DNR accumulation when no calcium antagonists were present but caused an increase in concentrations of calcium antagonists needed to promote DNR accumulation. It appeared that DNR accumulation in suspended cells correlated well with cytotoxicity assays, performed on cells growing in monolayer in 96-well microtiter plates, when accumulation was measured in medium with the same protein constitution as in growth medium (10% fetal calf serum). It is concluded that protein binding effects should be taken into account in the screening of compounds for the circumvention of multidrug resistance.
Antibiotics, Antineoplastic↗
Endocrine tumors.
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3-Iodobenzylguanidine↗