[Carboxypeptidase-G2-rescue in a woman with methotrexate-induced renal failure]. / Carboxypeptidase-G2-Rescue bei einer Patientin mit Methotrexat-induziertem Nierenversagen.

BACKGROUND: Methotrexate (MTX) is a very effective chemotherapeutic drug, widely used in various malignant diseases for systemic therapy. In some cases, MTX-induced renal failure occurs which may not be prevented by the standard agent folin acid as a specific antidot. This results in a MTX-accumulation in the body tissue with subsequent massive toxic side effects. CASE REPORT: We report on a 62-year-old woman with acute lymphoblastic leukemia (first diagnosis November 1997) receiving chemotherapy with 2,340 mg methotrexate over 24 hours. After an increase of the MTX-plasma-level 36 hours following MTX-application, increased serum creatinine levels (maximum 5.07 mg/dl) were found. The application of folinic acid was without any significant effect. Fifty-six hours following MTX, 50 U/kg carboxypeptidase-G2 was infused. The MTX-plasma-level decreased rapidly and a recovery of renal function was monitored. CONCLUSION: CPDG2 may be highly effective in patients after development of an MTX-induced renal failure and delayed MTX-excretion.

[Hemorrhagic diathesis as initial symptom of stomach carcinoma]. / Hämorrhagische Diathese als Erstsymptom eines Magenkarzinoms.

BACKGROUND: Microangiopathic hemolytic anemia (MAHA) and disseminated intravasal coagulation (DIC) as initial paraneoplastic symptoms of a solid tumor present a rare clinical situation. CASE REPORT: In 1998 a female patient was admitted due to multiple thrombosis, thrombocytopenia and fever. The initial diagnostic procedures revealed peri-aortic lymphomas and a tumor bulk (7 x 8 cm) in the upper abdomen. Gastroscopy revealed a 2 cm ulcer at the back side of the gastric corpus. Histologically, a signet-ring cell carcinoma was diagnosed. Final diagnosis stated a multilocular metastasising gastric cancer with infiltration of bone, peritoneum and dura and signet-cell infiltration of the bone marrow. Hematologic investigation in view of multiple paraneoplastic thrombosis revealed a microangiopathic hemolytic anemia associated with disseminated intravasal coagulation. Parallel to initial symptomatic therapy of coagulopathy, systemic cytostatic therapy with CDDP and VP-16 was initiated. In addition, radiotherapy of the brain was performed. After histologic confirmation of the diagnosis, weekly therapy with 5-FU (2600 mg/m2) and folinic acid (500 mg/m2) according to the Ardalan protocol was performed. After first signs of moderate response, oxaliplatin (60 mg/m2, day 1) was added. Although the chemotherapy dose had to be reduced due to prolonged neutropenia, the disturbances of hemostasis resolved completely resulting in reduced substitution rates with fresh frozen plasma (FFP) and platelets. Unfortunately, the patient died at home due to pulmonary embolism. CONCLUSION: Tumor-associated hemostaseologic alteration requires immediate substitution of FFP and platelets. However, it should be followed by specific therapy of malignancy, since tumor-induced metabolites (e.g. mucin) maintain the alteration of hemostasis. Chemotherapy may therefore be the best strategy to prevent complications such as MAHA and DIC.

Human hematopoietic growth factors: old lessons and new perspectives.

Erythropoietin (EPO), granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage stimulating factor (GM-CSF) are currently licensed for use in cancer patients and play a significant role in the management of anemia and neutropenia following myeloblative chemotherapy. EPO was the first recombinant hematopoietic growth factor to be used clinically after a number of clinical trials which demonstrated its effectiveness in treating mild to moderate cancer-associated anemia with or without concomitant chemotherapy (particulary cisplatin). An extensive research has been made for the improvement of the quality of life with EPO therapy, however, when formally assessed, variable effects of this important treatment have been observed. Recently, EPO has been shown to significantly accelerate hematopoietic reconstitution after peripheral blood stem cell transplantation (PBSCT) resulting in reduced infection rates. Both, G-CSF and GM-CSF have been shown, in numerous trials, to shorten the period of chemotherapy-induced neutropenia, with reduction in attendant morbidity and to mobilize PBSC. In addition, administration of both cytokines after PBSCT significantly reduced the use of antibiotics and duration of hospitalization suggesting an economic benefit. The narrower therapeutic window of GM-CSF at higher doses accounts for the fact that it is used much less frequently than G-CSF. To date, none of the growth factors used clinically has been shown to stimulate thrombopoiesis. Although thrombopoietin (TPO) has been found to induce megakaryocyte differentiation in vitro, it is unlikely to enter routine clinical use for treatment of post-chemotherapy thrombocytopenia, since results of clinical trials are not very encouraging, mainly because TPO is difficult to schedule and platelet aggregation may occur. Recently, innovative chimeric growth factor receptor agonists have been synthesized. Synthokine (SC-55494) (a high-affinity human IL-3 receptor ligand analog), myelopoietin (MPO) (activates human IL-3 and G-CSF receptors) and promegapoietin (PMP) (stimulates the human IL-3 and c-mpl receptors) were found to be multilineage hematopoietic growth factors and are currently undergoing clinical trials. Preliminary results suggest that these compounds may have a major impact on the management of myeloablative chemotherapy because of their ability to enhance platelet recovery in addition to their neutrophil restorative activity.

[Radiological evaluation of complications of implantable venous access port systems]. / Radiologische Dokumentation von Komplikationen implantierbarer venöser Portsysteme.

OBJECTIVE: Clinical signs and symptoms sometimes throw suspicion on functional complications and venous thrombosis due to implantable venous access ports. Objective was to determine frequency of these problems using radiologic imaging. METHODS: 61 patients were examined by means of fluoroscopy. If indication was given we injected radiopaque (contrast) medium. In the case of suspected vascular thrombosis the radiological finding was verified by sonography, phlebography or by venous magnetic resonance imaging angiography. RESULTS: Altogether 46 complications were documented in 37 out of 61 examined patients (61%). Occlusions of port-catheter were proved in 24 cases. It was the radiologically most frequently recorded complication (52%;) and found coincident with other problems in 9 patients (37%;). Pain frequently indicates break of catheters. Implantation of catheters into jugular and axillary veins predisposes to break of catheters just as port-catheters lateral implanted into subclavian veins ("pinch-off-sign"). CONCLUSIONS: Functional tests of venous access systems using fluoroscopy and phlebography give information that helps to decide if clinically problematic port-systems should be used furthermore. Directions of catheter which are predestined to complications should be avoided.

[Eosinophil cationic protein in a 39-year-old patient with Churg-Strauss syndrome]. / Eosinophiles kationisches Protein bei einer 39jährigen Patientin mit Churg-Strauss-Syndrom.

HISTORY AND CLINICAL FINDINGS: A 39-year-old woman in good health suddenly developed painful paraesthesia and incomplete paresis of all four limbs. Furthermore, arterial hypertension and tachycardia were found. The patient reported a history of chronic allergic rhinitis for 10 years and asthma one year. INVESTIGATIONS: Laboratory data showed an increased leucocyte count with a substantial increase in eosinophils in peripheral blood as well as in bone marrow. Nonspecific inflammatory markers such as erythrocyte sedimentation rate, C-reactive protein, fibrinogen as well as eosinophil cationic protein (ECP) were also increased. Histological investigations of a skin-muscle biopsy of the quadriceps revealed necrotizing vasculitis with extravascular granulomata and histiocytic giant cells. DIAGNOSIS, TREATMENT AND COURSE: Based on the diagnosis of Churg-Strauss syndrome treatment with methylprednisolone (500 mg every second day) was started, but was found to be ineffective after 10 days. Symptoms responded well to a subsequent course of 150 mg cyclophosphamide combined with 50 mg prednisolone per day. Pareses and pain were significantly reduced and all qualitative nerve functions returned to normal within two weeks of treatment. Laboratory parameters, especially the ECP, were similarly normalized. CONCLUSION: Churg-Strauss syndrome should be considered in the differential diagnosis of unexplained polyneuropathy. Determination of ECP may not only help in the diagnosis but does also facilitate monitoring of treatment and of further course of the disease.