Sentinel lymph node procedure with the combined technique is highly accurate in predicting the inguinofemoral lymph node status in patients with early-stage vulvar cancer. Future trials should focus on the safe clinical implementation of the sentinel lymph node procedure in these patients. Step sectioning and immunohistochemistry slightly increase the sensitivity of detecting metastases in sentinel lymph nodes and should be included in these trials.

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Summary 9gmTc-sestamibi (SSmTc-MIBI) is a substrate for the P-glycoprotein (P-gp) pump but it is not known whether it is a substrate for the multidrug resistance-associated protein (MRP) pump. Therefore, 99mTc-MIBI was evaluated in the GLC4 cell line and its doxorubicin-resistant MRP-, but not P-gp-, overexpressing GLC4/ADR sublines as well as in the Si cell line and its MRP-transfected subline Sl-MRR 99mTc-MIBI concentration decreased in the GLC4/ADR sublines with increasing MRP overexpression and was lower in S1-MRP than in Si. 99mTc-MIBI plus vincristine increased 99mTc-MIBI concentration in GLC4 lines compared with 99,"Tc-MIBI alone. 99,"Tc-MIBI efflux raised with increasing MRP expression in the GLC4 lines. Glutathione depletion elevated 99mTc-MIBI concentration in GLC4/ADR15,x. Cross resistance for 99Tc-MIBI, used to test cytotoxicity of the Tc compound, was observed in GLC4/ADR,50X vs GLC4. 99Tc-MIBI induced a synergistic effect on vincristine cytotoxicity in GLC4/ADR15oX. These results show that 99mTc-MIBI is involved in MRP-mediated efflux. The fact that 99mTc-MIBI efflux is influenced by MDR1 and MRP expression must be taken into account when this y-rays-emitting complex is tested for tumour efflux measurements.Keywords: multidrug resistance; P-glycoprotein; multidrug resistance-associated protein; 99mTc-sestamibi; drug transportResistance of tumours to chemotherapeutic compounds is an important problem in the clinic. Drugs such as anthracyclines, vinca alkaloids and epipodophyllotoxins are involved in the socalled multidrug resistance (MDR) Bradley et al, 1988;De Vries et al, 1989;De Jong et al, 1990;Meijer et al, 1990;Cole et al, 1992;Versantvoort et al, 1992; Scheper et al, 1993).One of the mechanisms involved in MDR is the overexpression, in tumour cells, of the ATP-dependent 170-kDa P-glycoprotein (P-gp) encoded by the MDR] gene (Endicott and Ling, 1989). P-gp acts as a transmembrane efflux pump that transports chemotherapeutic compounds out of the cell, resulting in drug resistance. P-gp is also expressed in many normal human tissues, such as the liver (bile canaliculi), pancreas, colon, jejunum and kidney (Thiebaut et al, 1987;Sugawara et al, 1988). In normal tissues, P-gp is considered to act as a transporter of toxins.Drugs that are substrates for P-gp are hydrophobic and mostly positively charged at neutral pH. Piwnica-Worms et al (1993) have shown that 99mTc-sestamibi (99mTc-MIBI), a lipophilic cationic radiopharmaceutical, is also a substrate for P-gp-mediated transport (Piwnica-Worms et al, 1993;Vallabhaneni et al, 1994;Ballinger et al, 1995). Consequently, 99-Tc-MIBI allowed visualization of P-gp-mediated efflux in tumours in the animal model (Piwnica-Worms et al, 1993).Apart from P-gp, another pump, the multidrug resistance-associated protein (MRP), is involved in MDR. The MRP pump was identified and characterized as a member of the ATP-binding cassette superfamily (Cole et al, 1992;Ishikawa, 1992 Correspondence to: EGE de Vries 1994). In MRP-transfected cell lines, it was shown that t...

Objective To evaluate the need for a bone scan as a routine staging procedure in patients with newly diagnosed prostate cancer in relation to serum prostate-speci®c antigen (PSA) and alkaline phosphatase (ALP) levels, and thus determine whether a reduction of the use of this staging method is possible in patients with a low probability of osseous metastasis. Patients and methodsThe results of bone scans were related retrospectively to levels of serum PSA and ALP in 363 patients with prostate cancer newly diagnosed between 1989 and 1997. Results Of 363 consecutive patients, 111 had a positive bone scan. In 19 of 144 (13%,`missed diagnosis') patients with a PSA level of <20 ng/mL the bone scan was positive. In 125 patients (49%,`false-positives') with a PSA level of >20 ng/mL the bone scan was negative. A threshold level of 100 U/L for ALP gave a better balance for the number of`false-positives' and missed diagnosis'. ALP values correlated better with an abnormal bone scan than did PSA levels; ALP levels of >90 U/L indicated a 60% chance for the presence of bone metastases. Conclusion Patients with newly diagnosed and untreated prostate cancer should undergo bone scintigraphy if there is bone pain or if ALP levels are >90 U/L. Recent reports discourage the routine use of a bone scan when the serum PSA level is <20 ng/mL. However, the present series suggests there is a greater chance of a positive bone scan in patients with low PSA levels; these ®ndings need further con®rmation.