Objectives. For patients with prostate specific antigen (PSA) values of 4-10 ng/mL, some urologists perform prostatic biopsies depending upon the findings of digital rectal examination (DRE) and transrectal ultrasonography (TRUS), and others perform biopsies on most of these men regardless of the findings of DRE and TRUS. The purpose of this study was to examine whether the information given by the measurement of the ratio of free to total (F/T) PSA can alter decision-making on prostatic biopsy. Methods. One hundred and two (102) men with PSA values between 4 and 10 ng/mL, were included in this study. All men were examined with DRE and TRUS; a F/T PSA ratio was also measured, and six prostatic biopsies were taken from each patient. Results. In 102 men who were biopsied, 22 (21.5%) prostatic carcinomas were identified. Among these 22 cancer patients, 13 had abnormal findings in DRE and/or TRUS and would have been biopsied and diagnosed anyway. If we use only the F/T PSA ratio (cut-off value 0.20) to decide whom to biopsy, we would have diagnosed 16/22 cancers; the difference between these two procedures was not statistically significant (P = 0.17). If we decide to biopsy those patients who have abnormal findings in DRE and/or TRUS and those who have a F/T PSA ratio <0.20, we would diagnose 20/22 cancers (P = 0.05) and at the same time, reduce the unnecessary biopsies from 80 to 41 (48%). With a PSA value between 4 and 10 ng/mL and no findings in DRE and TRUS and at the same time with a F/T PSA ratio ≤0.20, we would have to perform biopsies in 20.5 men to find one cancer. On the other hand, in patients with suspicious findings in DRE and/or TRUS and a F/T PSA ratio <0.20, in every two men that we biopsy we would find one cancer. Conclusion. We believe that among patients with PSA values between 4 and 10 ng/mL after performing DRE and TRUS, the additional information of F/T PSA ratio can help since it increases the number of cancers detected and reduces the number of unnecessary biopsies.

Anaplastic large cell lymphoma (ALCL) is a distinct clinicopathologic variant of intermediate grade non-Hodgkin's lymphomas (NHL) composed of large pleomorphic cells that usually express the CD30 antigen and interleukin (IL)- 2 receptors, and is characterized by frequent cutaneous and extranodal involvement. With variable frequency ALCL bear the t(2;5)(p23;q35) chromosomal translocation that fuses the nucleophosmin (NPM) gene on chromosome 5q35 to a novel protein kinase gene, Anaplastic Lymphoma Kinase (ALK), on chromosome 2p23. We determined the frequency of this translocation with e novel DNA polymerase chain reaction (PCR) technique using 0.5 μg of genomic DNA, 5'-primers derived from the NPM gene and 3'-primers derived from the ALK gene and hybridization with internal probes. The presence of amplifiable DNA in the samples was tested with the inclusion in the PCR reaction of oligonucleotide primers designed to amplify a 3016-bp fragment from the β-globin locus. NMP-ALK fusion amplicons were detected using DNA isolated either from all three ALCL cell lines tested, or from all four primary ALCL tumors known to contain the t(2;5)(p23;q35) translocation. Nested amplicons were detected by hybridization in 100% of specimens diluted 104-fold and in 20% of those diluted 105-fold. We subsequently examined archival genomic DNA from 20 patients with ALCL, 39 with diffuse large cell, 2 with mantle cell, 20 with peripheral T cell, 13 with low-grade NHL, 31 with Hodgkin's disease (HD), and 6 with lymphomatoid papulosis. Fusion of the NPM and ALK genes was detected in three of 18 patients with ALCL who had amplifiable DNA (17%, 95% confidence intervals 4% to 41%), but not in any patients with other NHL, HD, or lymphomatoid papulosis. The amplicon sizes were different in all cell lines and patients reflecting unique genomic DNA breakpoints. We conclude that with genomic DNA-PCR the rearrangement of the NPM and ALK loci is restricted to patients with ALCL. Further studies are needed to determine the prognostic significance of the NPM-ALK rearrangement, to determine whether its detection can aid in the differential diagnosis between ALCL, Hodgkin's disease, and lymphomatoid papulosis, and to establish the usefulness of the genomic DNA PCR in the monitoring of minimal residual disease in those patients whose tumors bear the t(2;5).

More effective and safer regimens are needed for patients who have advanced multiple myeloma resistant to or relapsing despite prior treatment with alkylating agents and VAD. We treated 58 such patients using the combination of twice daily cyclophosphamide (total dose 1.8 g/m2) and VAD (hyperCVAD). Treatment was given to outpatients followed by G-CSF at 5 μg/kg/d until granulocyte recovery. Twenty-three patients responded (40%), with a median duration of granulocyte depression to less than 500/μl of 4 days and a mortality rate of 2%. The median survival time for all patients was 15 months, and the median remission time of responding patients was 8 months. Patients who had low LDH, low B2M, or primary resistant disease lived significantly longer than patients without these features. The combination of fractionated cyclophosphamide and VAD provided an effective and safe rescue treatment for many patients who had advanced myeloma resistant to standard therapies.

Purpose: We assessed the incidence, clinical and radiological features, and prognosis of patients with renal lymphoma. Materials and Methods: We studied 210 patients with symptoms, signs and radiological findings suggestive of renal cell carcinoma. Results: Final diagnosis in 6 of 210 patients (3%) was primary renal lymphoma. Radiological features were similar to those of renal cell carcinoma. Five of the 6 patients had an International Prognostic Index score of greater than 1. Despite appropriate chemotherapy, only 2 patients remain with complete remission. Conclusions: Primary renal lymphoma is unusual but not rare. The relatively poor prognosis in our patients could be attributed to the adverse prognostic factors associated with aggressive nodal lymphomas.

Background. Skeletal complications are a major clinical manifestation of multiple myeloma. These complications are caused by soluble factors that stimulate osteoclasts to resorb bone. Bisphosphonates such as pamidronate inhibit osteoclastic activity and reduce bone resorption. Methods. Patients with stage III multiple myeloma and at least one lytic lesion received either placebo or pamidronate (90 mg) as a four-hour intravenous infusion given every four weeks for nine cycles in addition to antimyeloma therapy. The patients were stratified according to whether they were receiving first-line (stratum 1) or second-line (stratum 2) antimyeloma chemotherapy at entry into the study. Skeletal events (pathologic fracture, irradiation of or surgery on bone, and spinal cord compression), hypercalcemia (symptoms or a serum calcium concentration ≥12 mg per deciliter [3.0 mmol per liter]), bone pain, analgesic-drug use, performance status and quality of life were assessed monthly. Results. Among 392 treated patients, the efficacy of treatment could be evaluated in 196 who received pamidronate and 181 who received placebo. The proportion of patients who had any skeletal events was significantly lower in the pamidronate group (24 percent) than in the placebo group (41 percent, P<0.001), and the reduction was evident in both stratum 1 (P=0.04) and stratum 2 (P=0.004). The patients who received pamidronate had significant decreases in bone pain and no deterioration in performance status and quality of life. Pamidronate was well tolerated. Conclusions. Monthly infusions of pamidronate provide significant protection against skeletal complications and improve the quality of life of patients with stage III multiple myeloma.

This is a brief presentation of the emerging molecular concept of prostate cancer as regards the diagnosis and staging of the disease, analysis of tumour response to hormone-depletion therapy, and the cellular mechanisms that underly progression of the organ-confined tumour toward systemic dissemination and inevitable lethal disease.

Fludarabine monophosphate (Fludara) is a purine analogue which entered clinical trials in 1982. Although inactive in solid tumors, Fludara has marked activity in indolent lymphoproliferative disorders. The exact mechanism of action of Fludara is uncertain. Fludara has been established as the most active single agent in chronic lymphocytic leukemia (CLL) in single arm and comparative clinical trials. The activity has been demonstrated in both previously treated and initially treated patients. Marked activity has been noted in patients with low grade lymphoma, in particular, those with a follicular morphology and in Waldenstrom's macroglobulinemia. Combinations of fludarabine with alkylating agents, anthracyclines, and anthraquinones have led to clinically useful combination approaches. The ability of fludarabine to modulate the levels of the triphosphate form of cytosine arabinoside (ara-C) in acute leukemia cells has led to the development of combinations of fludarabine and ara-C. These combinations have demonstrated marked activity in treatment of relapsed and previously untreated patients with acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS). The ability to modulate the activity of pyrimidines and to inhibit repair of DNA damage caused by alkylating agents, anthracyclines, and other DNA active drugs suggest that the future of fludarabine will be in combination approaches to modulate the activity of other agents. These activities may extend its role to use in solid tumors.