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  • 1
    ISSN: 1432-1440
    Keywords: Metastatic ileal carcinoid ; Somatostatin analogue SMS 201–995 ; Tumor regression
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A 53-year-old man with metastatic ileal carcinoid ultimately failed to respond to conventional measures of surgery and was finally treated with a new long acting somatostatin analogue, SMS 201–995 for 7 months. SMS 201–995 not only gave symptomatic relief but also induced a reduction in metastatic tumor mass.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1440
    Keywords: Cerebral malaria ; Thrombomodulin ; Adhesion molecules ; Soluble interleukin-2 receptor ; Endothelial cell injury
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Severe Plasmodium falciparum malaria is characterized by multiple organ involvment due to sequestration of infected erythrocytes in small vessels. Endothelial cell adhesion molecules play an important role in this interaction. During the course of a severe cerebral P. falciparum malaria infection we found very markedly elevated levels of the soluble adhesion molecules intercellular adhesion molecule-1, E-selectin, and vascular cell adhesion molecule-1, with a maximum increase of nine, seven, and eight times, respectively. These very high levels of soluble adhesion molecules point to an endothelial cell injury as an additional cause to physiological release or shedding due to receptor interactions. Soluble thrombomodulin (sTM) levels showed an extremely marked elevation up to 332 ng/ml (up to 13 times the normal value) as well. Malaria patients without severe organ involvement/cerebral manifestation showed only a mild elevation of sTM levels. TM is a parameter independent of the immunological system. It is regarded as a marker of vasculitis and endothelial cell destruction. Therefore, markedly elevated sTM levels document a substantial endothelial cell injury in severe malarial infection and may be of diagnostic and prognostic importance.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0584
    Keywords: Granulocyte-macrophage colony-stimulating factor ; Neutropenia ; Thrombocytopenia ; Testicular cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Despite the increasing use of granulocyte-macrophage colony-stimulating factor (GM-CSF) for the treatment of chemotherapy-induced neutropenia, few studies have focused on the activity and toxicity of the different clinically used dosages of GM-CSF. Forty-four patients with “poor-risk” (advanced disease, according to the Indiana University classification) testicular cancer were treated with a dose-intensified chemotherapy regimen of cisplatin (30 mg/m2), etoposide (200 mg/m2), and ifosfamide (1.6 g/m2), given on days 1–5 for a total of four cycles at planned intervals of 21 days. Patients (pts) received GM-CSF, either 10 (22 pts; 70 cycles evaluable) or 5 μg/kg body wt. daily s.c. (22 pts; 72 cycles evaluable), starting the first day after chemotherapy for 10 consecutive days. Overall, 34 patients (78%) achieved a favorable response (CR or PR with negative tumor markers), six patients (14%) failed this chemotherapy regimen, and four patients (9%) died of therapy-related complications. The durations of both neutropenia and thrombocytopenia increased with the number of treatment cycles given. The duration of granulocytopenia after the fourth PEI cycle was significantly shorter for patients receiving 10 μg/kg than for those with 5 μg/kg per day of GM-CSF (9 vs 13 days;p〈0.05). The median duration of thrombocytopenia 〈20000/μl after the fourth cycle of PEI was also significantly reduced in favor of patients receiving 10 μg/kg of GM-CSF (4 vs 9 days;p〈 0.02). However, there were no differences in the frequency of severe infections or in the achieved dose intensity. Five patients (11%) discontinued GM-CSF due to side effects (three anaphylactoid-type reactions, one myalgia and fever, one cutaneous toxicity). No difference in the frequency of side effects was seen between patients receiving 5 and those receiving 10 μg/kg per day of GM-CSF. The dose of 5 μg/kg per day of GM-CSF may be sufficient to ameliorate neutropenia following standard-dose chemotherapy, while higher dosages of GM-CSF may be advantageous in patients receiving repetitive cycles of dose-intensified chemotherapy.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0584
    Keywords: CML ; Busulfan ; Hydroxyurea ; Interferon-alpha ; Duration of chronic phase ; Prospective study
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary For palliative therapy during the chronic phase of CML busulfan has proved to be the drug of choice. During the past years hydroxyurea and also interferon-alpha have gained increasing significance since they might prolong the duration of the chronic phase. In a multicenter study it is being determined, whether the use of hydroxyurea or of interferon-alpha instead of busulfan prolongs the duration of the chronic phase of Philadelphia positive CML. Additional goals are the examination of whether the types of disease evolution and the terminal phases differ between the treatment groups, and the prospective recognition of prognostic criteria for the duration of the chronic phase of CML. By December 31, 1987, 326 CML-patients had been randomized, 150 for busulfan, 150 for hydroxyurea and 26 for interferon-alpha. The average age is 50 years. 59 patients reached the end of the chronic phase, 55 died. The mean observation time of all patients is 1.34 years. At present no significant difference in survival is recognizable between the busulfan and hydroxyurea groups. Fewer adverse effects have been observed in the hydroxyurea group. Philadelphia chromosome negative patients show a higher average age and tend to have lower white blood cell and platelet counts. The number of patients having received interferon-alpha is still too small to allow evaluation. This report intends to document organization and progress of this study which to our knowledge is, at present, the largest ongoing prospective multicenter study on the therapy of CML.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-1335
    Keywords: Testicular cancer ; GM-CSF ; Cisplatin ; Etoposide ; Ifosfamide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In order to develop a more dose-intensive induction regimen for the treatment of far-advanced testicular tumours, the German Cooperative Group for Testicular Tumours started a dose-escalation trial of cisplatin, etoposide and ifosfamide. At the first dose level 18 patients with advanced testicular cancer (Indiana University classification) received cisplatin 25 mg/m2, etoposide 120–150 mg/m2 and ifosfamide 1.2 g/m2 for 5 days every 3 weeks. Of these, 13 patients (72%) became tumour-free, 2 achieved a stable, marker-negative partial remission, 2 had progressive disease and 1 patient died ofClostridium sepsis. The main toxicity was myelosuppression with a white blood cell nadir of 900/μl and a thrombocyte nadir of 47000/μl. Granulocytopenic fever occurred in 43% of all cycles. At the second dose level 15 patients received cisplatin 30 mg/m2, etoposide 150 mg/m2 and ifosfamide 1.6 g/m2 five times every 3 weeks together with s.c. recombinant granulocyte/macrophage-colony-stimulating factor (GM-CSF) 10 μg/kg on days 6–15. Acute toxicity was severe with a white blood cell nadir of 300/μl and thrombocyte nadir of 11 000/μl. The duration of the thrombocytopenia increased with cycle number; 63% of all cycles were associated with granulocytopenic fever and in 83% platelet transfusions were required. One patient died from acute renal failure andAspergillus sepsis; 3 patients experienced adverse reactions to GM-CSF, requiring omission of this drugs in 2; 33% had grade 3 or 4 mucositis. At this dose level 8 patients (53%) became tumour-free, 4 patients (26%) had marker normalization with irresectable residual disease and 2 patients were treatment failures. Though acute toxicity was severe at this dose level, there was no unexpected or unmanageable organ toxicity and thus patients are now entered at dose level 3, which consists of cisplatin 30 mg/m2, etoposide 200 mg/m2 and ifosfamide 1.6 g/m2 for 5 days and GMCSF 10 μg kg−1 day−1 on days 6–15 s.c.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Langenbeck's archives of surgery 379 (1994), S. 353-357 
    ISSN: 1435-2451
    Keywords: Colorectal carcinoma ; Adjuvant chemotherapy ; Adjuvant radiotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung In der Arbeit werden bisherige und aktuelle Konzepte der adjuvanten Chemo- und Radiotherapie in einer Übersicht dargestellt. Nach frühen Chemotherapiestudien mit systemischem Einsatz verschiedener Einzelsubstanzen folgten Versuche, die therapeutische Effizienz durch Wirkstoffkombinationen zu steigern. 5-FU erwies sich als relativ wirkungsvollste Einzelsubstanz, 5-FU/MeCCNU/Vincristin als wirksamste Kombination. Verbesserungen der Fünfjahresüberlebensraten konnten nur vereinzelt erzielt werden. Einen deuthchen Fortschritt erbrachte die Modulation der 5-FU-Wirkung durch Levamisol (LEV). Hierdurch wurde fur Kolonkarzinome im Stadium Dukes C eine Verbesserung der Fünfjahres-überlebensrate um 33% erzielt. Basierend auf diesen Daten wird empfohlen, alle Kolonkarzinompatienten im Stadium III mit 5-FU/LEV zu behandeln, soweit sie nicht einer aktuellen Adjuvansstudie zugeführt werden können. Der Empfehlung kann his heute noch keine weitere allgemeine Richtlinie hinzugefügt werden. Beim Rektumkarzinom kann durch prdoperative Radiotherapie ein Down-Staging nach Dosen von 35-45 Gy erzielt werden. Eine signifikant positive Beeinflussung der Überlebens-prognose ist jedoch weder durch eine alleinige prä- noch postoperative adjuvante Bestrahlung überzeugend dokumentiert. Demgegenüber konnten durch kombinierte postoperative Radio-Chemo-Therapien (5-FU/MeCCNU) sowohl verbesserte Überlebensraten als auch eine verbesserte lokale Tumorkontrolle im Vergleich mit der alleinigen Resektion aufgezeigt werden. Es besteht die Empfehlung, alle Rektumkarzinompatienten im Stadium II und III einer kombinierten Radio-Chemo-Therapie unter Studienbedingungen zuzuführen. Als effektivste Chemotherapie in Verbindung mit Radiatio gilt 5-FU/MeCCNU. Interimsergebnisse deuten jedoch darauf hin, daß MeCCNU verzichtbar ist. Die intraoperative Radiatio (IORT) erlaubt eine Dosiseskalation zur Optimierung der lokalen Tumorkontrolle bei maximaler Schonung strahlensensibler Strukturen. Bisher liegen noch wenig Ergebnisse vor. Eine generelle Wertung der IORT im Rahmen adjuvanter Konzepte ist noch nicht möglich. Die bisherigen Daten sind jedoch erfolgversprechend.
    Notes: Abstract A review is given of the historical and current concepts of adjuvant chemo- and radiotherapy of colorectal cancer. Early studies analyzing the use of single drug regimens were followed by a second study generation investigating adjuvant chemotherapeutic combinations. 5-FU proved to be the most efficient single drug investigated and 5-FU/MeCCNU/vincristin the most efficient chemotherapeutic combination, but no significant improvement in 5-year survival rates was achieved. Clear progress was noted with the introduction of levamisol (LEV) for modulation of 5-FU. A 33% improval in the 5-year survival rate in patients with stage III colon carcinoma was documented. It was therefore recommended (NIH consensus conference 1990) that all patients with stage III colon carcinoma be treated with this regimen unless admitted to other trials of adjuvant therapy. Preoperative radiotherapy with a dosage of 35–45 Gy can lead to downstaging of rectal cancer. Nevertheless, significant improvement in patient survival has not been proved convincingly using either isolated pre- or postoperative adjuvant radiotherapy. However, combined radiochemotherapy has been shown to improve both patient survival and local tumor control compared to surgical resection alone. It is therefore recommended that all stage II and III rectal cancer patients be treated with adjuvant combined radiochemotherapy. 5-FU/MeCCNU is currently expected to be the most efficient chemotherapy in combination with radiotherapy. Early data point out that MeCCNU could possibly be omitted. Intraoperative radiotherapy (IORT) allows further dosage escalation in order to improve local tumor control without affecting radiosensitive structures. Available data are still sparse and mostly based on the treatment of advanced carcinoma. A general validation of IORT is not yet possible, but current data are promising.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1435-2451
    Keywords: Esophageal carcinoma ; Operative therapy ; Preoperative (neoadjuvant) chemotherapy ; Oesophagus-carcinom ; Operative Therapie ; Preoperative Therapie
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung 42 Patienten mit nicht fernmetastasiertem Plattenepithel-Carcinom des Oesophagus wurden präoperativ cytostatisch vorbehandelt (Kelsen-Schema). Bei 18 Patienten kam es zu einer partiellen, bei 2 Patienten zu einer vollständigen Tumorremission. Von 40 Patienten, die sich einem operativen Eingriff unterzogen, waren 4 inoperabel. Bei 14 Patienten konnte der Tumor palliativ und bei 22 potentiell kurativ entfernt werden. Postoperativ verstarben 4 der 36 resezierten Patienten. Eine Anastomoseninsuffizienz trat bei 5 Patienten und schwere kardio-pulmonale Komplikationen bei 4 Patienten postoperativ auf. Die Nebenwirkungen der präoperativen Behandlung waren akzeptabel und werden durch das Ergebnis der Behandlung mit einer hohen Resektabilitätsrate und einer Verbesserung der Überlebenszeit von Patienten, die auf die präoperative Chemotherapie ansprechen, gerechtfertigt.
    Notes: Summary 42 patients with localized squamous cell carcinoma of the esophagus were treated according to a phase II study with cisplatin, vindesine and bleomycin (KelsenSchema) prior to surgery. In 18 of these patients partial remission was achieved and in two cases complete remission. Of the 40 patients which were presented to surgical treatment, 4 were inoperable, in 22 cases the tumor was removed in a potentially curative manner and in 14 patients a palliative resection was performed. The postoperative mortality was 4 of 36 resected patients. Anastomotic leakage was found in 5 patients and severe cardiopulmonary complications in 4 patients. The side effects of the preoperative treatment were acceptable and seem justified by the high resectability rate and the significant improvement in survival of patients who responded to chemotherapy.
    Type of Medium: Electronic Resource
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