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.

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.

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.

Rituximab-EPOCH, an effective salvage therapy for relapsed, refractory or transformed B-cell lymphomas: results of a phase II study.

BACKGROUND: Relapsed or refractory diffuse large B-cell and mantle-cell lymphoma have a poor prognosis. The EPOCH regimen and rituximab monotherapy have demonstrated activity as salvage therapies. Because of their non-overlapping toxicity, we evaluated their combination as salvage therapy in a phase II study. PATIENTS AND METHODS: Patients with relapsed or refractory CD20-positive large B-cell and mantle-cell lymphoma were offered treatment with rituximab 375 mg/m2 intravenously (i.v.) on day 1, doxorubicin 15 mg/m2 as a continuous i.v. infusion on days 2-4, etoposide 65 mg/m2 as a continuous i.v. infusion on days 2-4, vincristine 0.5 mg as a continuous i.v. infusion on days 2-4, cyclophosphamide 750 mg/m2 i.v. on day 5 and prednisone 60 mg/m2 orally on days 1-14. RESULTS: Fifty patients, with a median age of 56 years (range 23-72), entered the study. Twenty-five had primary diffuse large B-cell lymphoma, 18 transformed large B-cell lymphoma and seven mantle-cell lymphoma. The median number of prior chemotherapy regimens was 1.7 (range one to four). The median number of treatment cycles was four (range one to six). Possible treatment-related death occurred in two patients. Objective responses were obtained in 68% of patients (28% complete responses, 40% partial responses). Nineteen patients received consolidating high-dose chemotherapy with autologous stem-cell transplantation. The median follow-up was 33 months. Three patients developed a secondary myelodysplastic syndrome. The median overall survival was 17.9 months; the projected overall survival at 1, 2 and 3 years was 66, 42 and 35%, respectively. The median event-free survival was 11.8 months; the projected event-free survival at 1, 2 and 3 years was 50, 30 and 26%, respectively. CONCLUSION: The rituximab-EPOCH regimen is effective and well tolerated, even in extensively pretreated patients with relapsed or refractory large B-cell lymphoma and mantle-cell lymphoma.

[Giant cell tumor of bone with rapid malignant course]. / Riesenzelltumor des Knochens mit rapid malignem Verlauf.

The case of a 28-year-old male patient with a locally aggressive lesion of the distal tibia is presented. Following the diagnosis of giant cell tumor of bone (GCT) on biopsy and curettage, a rapid malignant course was observed with recurrence 2.5 months later. Multiple metastases appeared 6 months after initial presentation. Following initial chemotherapy according to the COSS protocol and later with carboplatin and VP-16, therapy was changed to Adriamycin and later gemcitabine due to progressive disease. Good palliation was achieved, and the patient felt well with less shortness of breath on exertion and was ambulatory with walking aids. The malignant nature of the tumor was not detected in the initial pathologic examinations. Review of the pathologic material provided histologic clues permitting the diagnosis of a primary malignant GCT with a fibrohistiocytic/fibrosarcomatous component. Malignancy in a giant cell tumor is a much debated diagnostic dilemma when a frank sarcomatous component is lacking. Cytologic atypias and flame-like tufts of infiltration of soft tissue are important clues. Surgical treatment should be commensurate. Monotherapy with Adriamycin or gemcitabine can be considered in order to inhibit the disease progression.

[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.

[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.

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.

Index of pretreatment intensity predicts outcome of high-dose chemotherapy and autologous progenitor cell transplantation in chemosensitive relapse of Hodgkin's disease.

PURPOSE: To identify prognostic factors in patients with chemosensitive relapsed Hodgkin's disease treated by high-dose chemotherapy with autologous progenitor cell transplantation (HDC) and to compare the duration of treatment-free remission prior to HDC with the progression-free survival after HDC in individual patients. PATIENTS AND METHODS: Forty-five consecutive patients were analyzed retrospectively. We devised an index of pretreatment intensity (IPTI) based number of different chemo- and radiotherapy regimens given between diagnosis and HDC and on the duration of disease. RESULTS: With a median follow-up of 47 months the post-transplant event-free survival (EFS) was 44% and the overall survival (OAS) was 62% at four years. The IPTI allowed to discriminate between a low and a high-risk group with a four-year post-transplant EFS of 66% and 11% and a OAS of 87% and 28%, respectively (P = 0.0001). Of the 39 patients with sufficient follow-up after HDC, post-transplant EFS lasted on average > or = 18.5 months longer than the pretransplant treatment-free remission. CONCLUSIONS: HDC with the CBV regimen confers significant benefit to patients with chemosensitive relapsed Hodgkin's disease. The IPTI may help to select patients with a good response to HDC and to identify poor prognosis patients suitable for experimental protocols or palliative care only.

Short-term weekly chemotherapy followed by high-dose therapy with autologous bone marrow transplantation for lymphoblastic and Burkitt's lymphomas in adult patients.

BACKGROUND: Type and duration of treatment for highly aggressive non-Hodgkin's lymphoma has been a matter of debate over the past decade. To determine the therapeutic efficacy of an abbreviated treatment regimen, 26 patients with newly-diagnosed highly aggressive lymphomas, 17 of them belonging to the International Working Formulation (IWF) group I and 9 with Burkitt's lymphoma (IWF J), were entered in a study using short-term weekly chemotherapy followed by high-dose therapy and autologous bone marrow transplantation. PATIENTS AND METHODS: Besides histology, requirements for entry into to the study were age between 16 and 60 years, stage 1 bulky disease and elevated LDH or stage II to IV disease with or without bulk or elevated LDH, and an absence of HIV infection or CNS involvement at diagnosis. The treatment plan was 12 weeks of MACOP-B or VACOP-B chemotherapy followed by high dose therapy and autologous bone marrow transplantation in first complete remission. RESULTS: Twenty patients (76%), 16 (62%) of those on MACOP-B or VACOP-B, 1 who had received 2 cycles of ProMACE-CytaBOM prior to MACOP-B and 3 after a first salvage regimen, achieved complete remissions. Seventeen patients (65%) were transplanted in first remission, and 15 (58%) after induction treatment with only MACOP-B or VACOP-B. Reasons for not being given high dose therapy and autologous bone marrow transplantation (ABMT) were failure to achieve complete remission in 6 patients, early relapse in 2 and severe pulmonary toxicity associated with chemotherapy in 1. The median time of follow-up was 45 months. At 3 years, the estimated event-free survival was 31% (CI 14%-50%) and the overall survival 48% (CI 25%-67%). There were no deaths from toxic effects of treatment. Pretreatment factors associated with relapse were stage III or IV disease, age over 30 years and bone marrow involvement. Logrank analysis showed that age was the only factor significantly associated with poor event-free survival. CONCLUSION: Short-term weekly chemotherapy followed by high-dose therapy with the CBV regimen in first remission is not a higly effective treatment for advanced lymphoblastic and Burkitt's lymphomas. The 30% rate of failure to achieve partial remission after 6 weeks and/or complete response after 12 weeks of MACOP-B or VACOP-B treatment, as well as the 42% failure rate to undergo ABMT in first remission, suggest that more aggressive chemotherapy should be used in the beginning.

[Participation in multicenter studies as quality control in the therapy of Hodgkin disease: an interim report]. / Teilnahme an Multizenterstudien als Qualitätskontrolle bei der Therapie des Morbus Hodgkin: ein Interimreport.

UNLABELLED: From 1988 to 1992 the Swiss Group for Clinical Cancer Research (SAKK) entered 113 patients with Hodgkin's disease into three stage adapted trials (HD-4-6) from the German Hodgkin Study Group (DHSG). In an interim analysis freedom from treatment failure (FFTF) and overall survival (OS) of the SAKK patients (SAKK-pt) were compared to the remaining study population (GHSH-pt) (median follow-up: 30 months for HD-4 and HD-5, 24 months for HD-6). RESULTS: HD-4: SAKK (n = 16), DHSG (n = 241), FFTF-SAKK: 100%, FFTF-DHSG: 85%, p: ns, OS-SAKK: 100%, OS-DHSG: 99%, p: ns, HD-5: SAKK (n = 66), DHSG (n = 639), FFTF-SAKK: 90%, FFTF-DHSG: 85%, p: ns, OS-SAKK: 93%, OS-DHSG: 95%, p: ns, HD-6; SAKK (n = 31), DHSG (n = 411): FFTF-SAKK: 62%, FFTF-DHSG: 68%, p: ns, OS-SAKK: 70%, OS-DHSG: 88%, p < 0.008. The results in the SAKK patients with advanced disease are unsatisfactory. Despite the fact that the treatment was given on time with full doses, 10/30 patients achieved no complete remission (CR). Only one patient relapsed after an initial CR. 6 patients had primary progressive disease. 6 patients died despite conventional salvage chemotherapy. High dose chemotherapy/autologous bone marrow transplantation (HDC/ABMT) was only given to 3 out of 8 potential candidates. Only 2/11 patients are still alive and disease-free after relapse or initial progression. Both had received HDC/ABMT as part of their salvage regimen. This interim analysis identifies a group of patients in which treatment strategies need to be optimized.

[5 years of dosage intensification and autologous bone marrow or peripheral stem cell transfusion in malignant lymphoma with a high risk of recurrence]. / Fünf Jahre Dosisintensivierung mit Rücktransfusion autologer Knochenmarksoder peripherer Stammzellen bei malignen Lymphomen mit hohem Rezidivrisiko.

Clinical results of the treatment of malignant lymphomas with a high risk of relapse by dose intensification and autologous bone marrow transplantation are reported. Since 1988, 68 patients with a median age of 34 years (range 16 to 56 years) received dose intensification, including 25 non-Hodgkin's lymphomas in first remission (12 lymphoblastic or Burkitt's lymphomas and 13 large cell lymphomas with risk factors), 20 aggressive non-Hodgkin's lymphomas in chemosensitive relapse, and 23 Hodgkin's lymphomas in chemosensitive relapse. The calculated 3-year overall survival and relapse-free survival was 72% (CI: 57-82%) and 61% (CI: 47-73%) respectively. Treatment related deaths were seen in 4.4%. The median duration of hospitalization was 30 days (range 19-51 days). The relapse-free 3-year survival for the separate treatment groups was 80% for lymphoblastic and Burkitt's lymphomas in first remission, 77% for large cell lymphomas with clinical risk factors in first remission, 39% for aggressive non-Hodgkin's lymphomas in chemosensitive relapse, and 59% for Hodgkin's lymphomas in chemosensitive relapse. These excellent results were obtained with acceptable toxicity and justify the use of dose intensification for a group of young patients with high risk lymphomas.

[Suspected adult-onset Still's disease: unexpected manifestation of leprosy]. / Vermeintlicher Morbus Still des Erwachsenen: unerwartete Manifestation einer Lepra.

A 23-year old male from Sri Lanka was admitted to hospital with symmetrical inflammatory peripheral polyarthritis, fever of 39 degrees C and poly-lymphadenopathy. At first we suspected adult onset Still's disease. The histological findings from axillary lymph node biopsy strongly suggested the diagnosis of leprosy, for which we had had little evidence thus far. Typical skin lesions were absent, skin smears were negative and neurological symptoms only became obvious much later when fever and arthritis had subsided under anti-inflammatory treatment. At this time a right ulnar palsy developed, with atrophy of the interosseous muscles and thickening of the ulnar nerves at both medial epicondyles. Fite-stains of a sural nerve biopsy confirmed the diagnosis when mycobacteria were detected. Leprosy displays a clinico-pathological spectrum caused by variations in host resistance. A widely accepted classification is the five group system of Ridley and Jopling. At one extreme of this spectrum are patients with lepromatous or low resistance leprosy with numerous bacilli, and at the other those with high resistance or tuberculous leprosy where few or no bacilli are found. The numerous bacilli in the sural nerve biopsy classified the disease as lepromatous in our case. Of the various manifestations of the lepra reaction occurring in lepromatous leprosy, one is acute arthritis, but a more common one is erythema nodosum leprosum. Our patient's clinical presentation was interpreted to be a rheumatic manifestation of a type-2 reaction. This form of immunological response in leprosy is an immune complex syndrome and may mimic different rheumatic diseases.(ABSTRACT TRUNCATED AT 250 WORDS)

Chemotherapy with MACOP-B and VACOP-B for intermediate- and high-grade non-Hodgkin's lymphoma: clinical results and analysis of prognostic factors.

Eighty-three previously untreated patients with aggressive non-Hodgkin's lymphomas were treated with either MACOP-B (23 patients) or VACOP-B (60 patients) as originally described by Klimo and Conners [1, 2]. Their median age was 46 years. Thirty-seven patients had stage I or II and 46 stage III or IV disease. The tumor histopathology was reviewed in all cases. Sixty-five patients had intermediate grade and 18 high-grade non-Hodgkin's lymphomas according to the International Working Formulation. The rate of complete response was 74% for MACOP-B and 76% for VACOP-B. At the time of analysis the duration of follow-up was 50 months for the MACOP-B and 22 months for the VACOP-B group. The actuarial three-year progression-free survival was 35 +/- 10% for the MACOP-B group, 48 +/- 11% for the VACOP-B group, and 46 +/- 7% for all patients. Treatment mortality was 6%. A univariate and a multivariate analysis of selected pretreatment parameters and of regimen demonstrated that stage III or IV, high-grade lymphoma, and elevated serum LDH, but not the type of regimen, are significantly associated with poor progression-free survival in our patient population.

[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.

Zürich experience with preoperative, high dose methotrexate-containing chemotherapy in patients with extremity osteosarcomas (OSA).

From 1979 to 1990, 37 patients with extremity osteosarcomas, 22 of them males and 15 females, median age 19 years, received pre- and postoperative chemotherapy. The period of observation, calculated from after the primary operation, ranged from 1-114 months, median 25 months. After preoperative chemotherapy, 9 (24%) underwent a primary amputation, in 28 (76%) a limb salvage procedure was possible, 4/29 (14%) later developed local recurrences, metastases were diagnosed in 8/9 amputees and 5/28 after limb-sparing surgery. The five-year disease-free and overall survivals after amputation are 11% and 33%, respectively, compared to 68% and 75%, respectively (p = 0.001 and 0.018, respectively, for long rank). Results of histologic assessment after preoperative chemotherapy are of significant prognostic impact. The earlier prognostic groups of 0%-49% necrosis versus 50%-100% necrosis were statistically no longer suitable for distinguishing useful prognostic groups. In this second analysis, patients with 0%-79% necrosis versus 80%-100% necrosis had 5-year disease-free survivals of 81% versus 44% (p = 0.032) and 5-year overall survivals of 88% In summary, 24% of our patients with extremity osteosarcomas, most of them with large primaries close to joints, had to undergo primary amputation and had only a 33% 5-yr-survival, whereas limb salvage procedures with pre-and postoperative chemotherapy were associated with a 5-yr survival of 75% and thus had no adverse impact. Careful selection of patients for successful management of osteosarcomas is important; necrosis of 80% and more after preoperative chemotherapy is a prerequisite for a favourable outcome.

[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.