Evaluation of a particle gel immunoassay as a screening test for syphilis.

BACKGROUND: Recent trends in Western Europe show an increase in sexually transmitted infections. Surveillance data in Switzerland confirm this rising trend. Notifications of syphilis cases nearly doubled in the year 2002 and almost tripled in 2003. This trend necessitates an early correct diagnosis making reliable screening tests mandatory. MATERIALS AND METHODS: In the presented study a particle gel immunoassay (ID-PaGIA syphilis antibody test, Diamed) using recombinant treponemal antigens TpN15, TpN17 and TpN47 was evaluated as a screening test in comparison to the currently used Treponema pallidum particle agglutination test (Serodia-TPPA, Fujirebio). Serum samples were obtained from a cross-sectional sero-epidemiological study among men who have sex with men. Samples were tested with the PaGia and the TPPA. In the case of equivocal results a titrated TPPA of an external laboratory was used as a confirmation test. RESULTS: In total 650 serum samples (48 seropositive patients, 602 negative) were evaluated. The PaGIA showed a sensitivity of 0.89 (43/48) and the TPPA of 0.83 (40/48). This difference was not statistically relevant (p = 0.4). The particle gel assay showed a significantly higher specificity (1.0) compared to the TPPA (0.98) (p = 0.004). CONCLUSION: The PaGIA showed a sensitivity comparable to that of other treponemal tests with an even better specificity. Advantages of the PaGIA are the fast reaction time of only 20 min and the simplicity of the procedure with minimal technical equipment.

Cisplatin, doxorubicin and etoposide (PAV) in advanced gastric carcinoma: the SAKK experience. Swiss Group for Clinical Cancer Research (SAKK).

EAP (etoposide, doxorubicin, cisplatin), a chemotherapeutic combination given over 8 days, proposed by German investigators in cancer of the stomach, has been considered to be too toxic by others. A positive experience with a similar regimen (PAV) developed by the SAKK given over 3 days in small cell lung cancer led us to test it in gastric adenocarcinoma. 41 patients with metastatic gastric cancer were enrolled in the study and 38 were evaluable for response and toxicity. One complete response and 12 partial responses were recorded, giving a response rate of 34% (95% confidence interval (CI) 20-51%). Median progression-free and overall survival were 3.4 and 6.3 months, respectively. Haematotoxicity was the leading toxicity with 34 (90%) and 17 (45%) grade III-IV neutropenia and thrombocytopenia, respectively. Despite this high rate of granulocytopenia, only six episodes of non-fatal febrile neutropenia were observed. Other toxicities were relatively easy to manage with infrequent grade III-IV occurrences. We conclude that PAV is active in gastric cancer and seems to be better tolerated than EAP.

Clinical experience with preoperative chemotherapy for osteosarcoma.

Since 1978 preoperative chemotherapy has been administered to 15 consecutive patients with osteosarcomas in Zurich. Preoperative chemotherapy was acceptably well tolerated and did not impair surgical procedures. Our retrospective analysis confirmed that the extent of necrosis after preoperative chemotherapy is of biological importance for the further course of the disease. Patients with extensive necrosis had better relapse-free survival and longer overall survival than those with little necrosis.

[Interdisciplinary team work from the viewpoint of the medical oncologist]. / Die interdisziplinäre Zusammenarbeit aus der Sicht des medizinischen Onkologen.

Collaboration of specialists is a prerequisite for the modern care of cancer patients. The 'tumor board' plays a central role. As a rule, close to 10% of all cancer patients of a hospital are reviewed by this panel. Patho-anatomic questions are settled and therapeutic plans established. A cooperative case review shortens decision paths, and therapeutic procedures are supported by all the participating specialists. The tumor board is also appreciated by postgraduate education, and it facilitates the introduction of oncologic thinking in the general hospital. For the specialist the incentive is to provide insight into his field, to expose advantages or weaknesses of his therapeutic modalities and to adapt them to the special needs of a particular patient.

Long-term results of a multicenter SAKK trial on high-dose ifosfamide and doxorubicin in advanced or metastatic gynecologic sarcomas.

BACKGROUND: Dose intensive chemotherapy has not been tested prospectively for the treatment of gynecologic sarcomas. We investigated the antitumor activity and toxicity of high-dose ifosfamide and doxorubicin, in the context of a multidisciplinary strategy for the treatment of advanced and metastatic, not pretreated, gynecologic sarcomas. PATIENTS AND METHODS: Thirty-nine patients were enrolled onto a phase I-II multicenter trial of ifosfamide, 10 g/m2 as a continuous infusion over 5 days, plus doxorubicin intravenously, 25 mg/m2/day for 3 days with Mesna and granulocyte-colony-stimulating factor every 21 days. Salvage therapy was allowed after chemotherapy. RESULTS: Among the 37 evaluable patients, the tumor was locally advanced (n = 11), with concomitant distant metastases (n = 5) or with distant metastases only (n = 21). After a median of three (range 1-7) chemotherapy cycles, six patients experienced a complete response and 12 a partial response for an overall response rate of 49% (95% CI 32% to 66%). The response rate was higher in poorly differentiated tumors (62%) compared with moderately well differentiated ones (18%), but was not different according to histology subtypes. Eleven patients had salvage therapy, either immediately following chemotherapy (n = 7) or at time of progression (n = 4). With a median follow-up time of 5 years, the median overall survival was 30.5 months. Hematological toxicity was as expected neutropenia, thrombopenia and anemia > or = grade 3 at 50%, 34% and 33% of cycles respectively. No toxic death occurred. CONCLUSIONS: High-dose ifosfamide plus doxorubicin is an active regimen for all subtypes of gynecological sarcomas. Its toxicity was manageable in a multicentric setting. The prolonged survival might be due to the multidisciplinary strategy that was possible in one-third of the patients.

Treatment of advanced soft-tissue sarcomas using a combined strategy of high-dose ifosfamide, high-dose doxorubicin and salvage therapies.

Having determined in a phase I study the maximum tolerated dose of high-dose ifosfamide combined with high-dose doxorubicin, we now report the long-term results of a phase II trial in advanced soft-tissue sarcomas. Forty-six patients with locally advanced or metastatic soft-tissue sarcomas were included, with age <60 years and all except one in good performance status (0 or 1). The chemotherapy treatment consisted of ifosfamide 10 g m(-2) (continuous infusion for 5 days), doxorubicin 30 mg m(-2) day(-1) x 3 (total dose 90 mg m(-2)), mesna and granulocyte-colony stimulating factor. Cycles were repeated every 21 days. A median of 4 (1-6) cycles per patient was administered. Twenty-two patients responded to therapy, including three complete responders and 19 partial responders for an overall response rate of 48% (95% CI: 33-63%). The response rate was not different between localised and metastatic diseases or between histological types, but was higher in grade 3 tumours. Median overall survival was 19 months. Salvage therapies (surgery and/or radiotherapy) were performed in 43% of patients and found to be the most significant predictor for favourable survival (exploratory multivariate analysis). Haematological toxicity was severe, including grade > or =3 neutropenia in 59%, thrombopenia in 39% and anaemia in 27% of cycles. Three patients experienced grade 3 neurotoxicity and one patient died of septic shock. This high-dose regimen is toxic but nonetheless feasible in multicentre settings in non elderly patients with good performance status. A high response rate was obtained. Prolonged survival was mainly a function of salvage therapies.

[High-dose chemotherapy with autologous bone marrow transplantation: 11 years' experience in Zurich]. / Hochdosis-Chemotherapie mit autologer Stammzelltransplantation: 11 Jahre Zürcher Erfahrung.

High-dose chemotherapy with autologous bone marrow or peripheral blood stem cell transplantation has gained widespread acceptance for the treatment of certain malignancies. Since the introduction of this therapy in 1988 we have treated 272 patients. Indications for high-dose chemotherapy were high-risk large cell lymphoma and lymphoblastic or Burkitt lymphoma in first remission (73 patients), non-Hodgkin's lymphoma in chemosensitive relapse (65 patients), Hodgkin's lymphoma in relapse (52 patients), germ cell tumours with inadequate response to chemotherapy (34 patients), multiple myeloma (29 patients), and other malignancies (19 patients). Treatment mortality was 1.8%. The 3-year event-free survival and overall survival for all patients were 48 and 61% respectively. High-dose chemotherapy with autologous stem cell transplantation has become a safe procedure and is considered the treatment of choice for relapsed large cell lymphoma, relapsed Hodgkin's disease, stage II or III multiple myeloma, and germ cell tumours with inadequate response to cisplatin-based chemotherapy. In other situations, including aggressive lymphoma with risk factors, acute leucaemia or breast cancer, the superiority of high-dose over conventional chemotherapy remains to be proven. Patients with such diseases should not receive high-dose chemotherapy outside a controlled clinical study.

[Hypercalcemia in non-Hodgkin lymphoma]. / Hypercalciämie bei Non-Hodgkin-Lymphomen.

In a retrospective study, hypercalcemia was found on one or more occasions in 14 of 156 patients with newly detected, still active or relapsing non-Hodgkin's lymphoma (NHL). The incidence of hypercalcemia correlated with the histological grade of malignancy: patients with high grade NHL had a hypercalcemia incidence of 23%. Half of the patients had hypercalcemia-related symptoms, and 4 of 14 had hypercalcemia-induced renal impairment. The occurrence or recurrence of hypercalcemia correlated with progression of NHL. Remission-inducing chemotherapy and symptomatic treatment of hypercalcemia corrected the serum calcium.

[Anagrelide in control of myeloproliferative thrombocythemia: long-term experiences in 6 patients]. / Anagrelide zur Kontrolle der myeloproliferativen Thrombozythämie: Langzeiterfahrung bei 6 Patienten.

Symptomatic or asymptomatic chronic elevation of platelet count can be observed in all forms of myeloproliferative disorders (MPD). Benefits and limitations of the traditional platelet-reducing agents, such as radioactive phosphorus, alkylating agents, hydroxyurea and interferon alpha, are well known and have been largely described. Anagrelide (Agrelin) is an additional newer drug with a selective platelet-lowering effect. We describe our own long-term experience in 6 patients with MPD who were treated with anagrelide as part of a compassionate-use protocol between April 1991 and August 1997. The median duration of therapy was 54 months (range 17 to 75 months), with an overall response rate of 100% (complete and partial response for at least 4 weeks). The initial median platelet count of 1211 x 10(9)/l (range 847 to 2050 x 10(9)/l) was reduced rapidly and lastingly to 570 x 10(9)/l (range 216 to 667 x 10(9)/l) at the time of the last control. Under treatment with anagrelide 4 of the 6 patients showed a reduction of disease-associated symptoms or complications. Adverse reactions were generally mild and transitory, and no interruption or cessation of therapy was required. Development of drug resistance or late adverse events were not observed. Treatment with anagrelide is effective, safe and in our opinion easy to administer. It also appears to be suitable for long-term administration.

[Liposarcoma of the laryngeal region. Case report and literature review]. / Liposarkom der Larynxgegend. Fallbericht und Literaturübersicht.

The case is reported of a 64-year-old man in whom a pedunculated tumor of the Vallecula epiglottica occurred and was excised. Histologically it proved to be a dedifferentiated liposarcoma. The patient is well and free of disease 18 months later. The literature is reviewed and 20 other cases of liposarcoma in the laryngeal region are discussed.

[Efficiency of the blood cell separator Haemonetic 30 in the separation of platelets from single donors]. / Leistungsfähigkeit des Blutzellseparators Haemonetic 30 bei der Plättchengewinnung aus Einzelspendern.

By means of the Haemonetic 30 separator we were able to collect 4.1 +/- 0.94 X 10(11) (X +/- 1 SD) platelets in 57 procedures consisting of 5-6 cycles. The platelet yield was significantly influenced by the blood volume processed and by initial platelet counts in donors. Augmenting platelet collection volume in the red colored part of the buffy-coat from 10-20 ml did not increase the yield. Transfusion of collected platelets into 27 non-sensitized patients showed normal recovery of 43% at one hour and shortening of bleeding time from over 30 min to a mean of 5 min 20 sec in 12 patients tested. Autotransfusion of 51Cr-labeled platelets into 8 healthy donors revealed identical recoveries (42 +/- 12%) and a normal survival time (9.2 +/- 0.7 days).

[Effectiveness and toxicity of high-dosage Ara-C. Clinical observations in 10 cases and review of the literature]. / Wirksamkeit und Toxizität von hochdosiertem Ara-C. Klinische Beobachtungen bei 10 Fällen und Literaturübersicht.

Ten patients with acute myeloid leukemia were treated with a high-dose ara-c regimen (3 g twice daily for 6 days). 5 patients (50%) achieved a complete remission lasting for a median duration of 5 months. These patients had all achieved a complete remission following standard treatment with ara-c. High-dose ara-c was ineffective in 2 patients resistant to standard ara-c protocols. The most important side effects of high-dose ara-c were conjunctivitis and cerebellar symptomatology. In one case a severe diffuse encephalopathy with cerebellar predominance set in at a remarkably late stage (45 days after starting treatment). Our results and those of other authors suggest that treatment with high-dose ara-c should be used with caution.

[Treatment of soft tissue sarcoma. A multidisciplinary approach]. / Le traitement des sarcomes des tissus mous. Une approche multidisciplinaire.

The treatment of soft tissue sarcomas is at present a multidisciplinary process. In Switzerland, patients are too often referred to specialized centers after an inadequate management. The general principles of biopsy, surgery, radiotherapy and chemotherapy are reviewed in the light of the biological behaviour of these tumors. Emphasis is made on the role of adjuvant chemotherapy that is not yet established and that is the subject of an ongoing Swiss Study. A collaboration to the study of the Swiss centers and the surgeons is needed in order to improve the quality of treatment of these tumors.

Effects of leukocyte interferon (E. coli) on human bone sarcoma growth in vitro and in the nude mouse.

Effects of highly purified human leukocyte interferon (rIFN-alpha 2) on colony formation, DNA synthesis and proliferation in nude mice of tumor cells from eight bone sarcomas have been studied. rIFN-alpha 2 produced a dose-dependent inhibition of [3H]thymidine incorporation by sarcoma cells. Even at high doses (10(4) U/ml), however, [3H]thymidine uptake could not be completely blocked by rIFN-alpha 2. In a cloning assay three established sarcoma cell lines and five other sarcoma samples obtained after short-term in vitro culture were found to be sensitive to various degrees to rIFN-alpha 2, complete inhibition being seen only at 10(4) U/ml. Three sarcomas were sensitive in the nude mouse model. Scheduling experiments revealed that rIFN-alpha 2 produces a delay in tumor growth only when administered either before or shortly after tumor implantation. Therefore rIFN-alpha 2 appears to be most active when tumor size is small and growth not exponential, indicating that rIFN-alpha 2 may play a role in an adjuvant setting. Growth sarcomas strongly suppressed by rIFN-alpha 2 in the cloning assay was markedly inhibited in the nude mouse. One sarcoma which was only moderately sensitive in the cloning assay was resistant in the animal experiment, confirming the predictive value of the clonogenic assay. Although the present findings demonstrate strong antitumor activity of rIFN-alpha 2 against human bone sarcoma cells they should be interpreted with caution mainly because the high rIFN-alpha 2 levels used in the experiments cannot be maintained in patients over a prolonged period.