Primary reexcision for patients with 'microscopic residual' tumor following initial excision of sarcomas of trunk and extremity sites

Among 404 patients with primary tumors of extremity-trunk sites entered in the Intergroup Rhabdomyosarcoma Study (IRS) (1972 to 1984), 154 were placed in clinical group IIa, ie, with negative nodes but with "microscopic residual" (MR) disease, following the initial excisional (not biopsy) procedure. An elective reexcision of the area of the primary tumor (PRE) was performed in 41 of these patients within 35 days (mean interval, 14 days; SE, 0.9) with no intervening therapy. These procedures consisted of wider excision of the tumor "bed," resulting in a technical transfer of these patients from group IIa to group I, ie, complete excision. This reduced intensity of nonsurgical therapy (irradiation and chemotherapy). Among the 41 patients who underwent PRE, the 3-year survival estimate (Kaplan-Meier) was 91% (SE, 4%). This may be compared with the results in 113 patients who remained in group IIa, in which the 3-year survival estimate was 74% (SE, 4%). A second group for comparison consisted of the 73 patients with trunk/extremity tumors who were placed in group I after a single excisional procedure, ie, no PRE, in whom the 3-year survival estimate was 74% (SE, 5%). Recognized prognostic factors influencing survival in these groups were comparable, with the exception of tumor size, ie, the largest tumors (greater than or equal to 10 cm in diameter) were concentrated in groups I and IIa. When patients with tumors greater than or equal to 10 cm in diameter (9.7% of the total) were removed from all three study groups, patients undergoing PRE had longer survival duration estimates than patients in the control groups.     

Role of mast cells in experimental anti-glomerular basement membrane glomerulonephritis

Recently, divergent reports on the role of mast cells (MC) in different glomerular diseases have brought our attention to their role in an accelerated model of anti-glomerular basement membrane (GBM) glomerulonephritis (GN). Genetically MC-deficient Kit(W)/Kit(W-v) mice, MC-reconstituted Kit(W)/Kit(W-v) mice and Kit+/+ control mice were subjected to anti-GBM GN. Kit(+/+) mice developed moderate proteinuria and glomerular damage following the induction of anti-GBM nephritis. In contrast, proteinuria and glomerular damage were dramatically increased in MC-deficient Kit(W)/Kit(W-v) mice. MC-reconstituted Kit(W)/Kit(W-v) mice showed proteinuria and glomerular damage comparable to Kit+/+ mice. A significant increase in infiltrating T cells and macrophages was detected in MC-deficient Kit(W)/Kit(W-v) mice as compared to Kit+/+ control mice and MC-reconstituted Kit(W)/Kit(W-v) mice. Accordingly, we observed an increase of TGF-beta1 mRNA in kidneys from Kit(W)/Kit(W-v) mice. Interestingly, we did not detect MC in the kidney using either Giemsa staining or RT-real-time PCR, but MC were found in the regional lymph nodes. Finally, mortality of Kit(W)/Kit(W-v) mice was significantly increased after the induction of anti-GBM GN due to uremia. Our report provides the first direct evidence that MC are protective in anti-GBM GN, possibly by modulating the influx of effector T cells and macrophages to inflammatory sites in the kidney.     

Effects of chemical mediators of anaphylaxis on ciliary function

We assessed the effects of selected chemical mediators of anaphylaxis on CBF in vitro. Ciliated epithelial cells were obtained from the trachea of conscious sheep with a cytology brush and suspended in a perfusion chamber containing KH. Ciliary activity was viewed microscopically and recorded on videotape for subsequent slow-motion analysis of CBF. Prostaglandin E1 (10(-8) M to 10(-6) M), prostaglandin E2 (10(-10) M to 10(-6) M), and leukotriene-C4 (10(-8) M) increased CBF between 7% and 33%. Histamine caused ciliostimulation only at the relatively high concentrations above 10(-5) M (7% increase in CBF), whereas prostaglandin F2 alpha (10(-10) M and 10(-6) M) was without effect. In no preparation was ciliary discoordination observed. These findings indicate that several chemical mediators of anaphylaxis stimulate CBF and that the previously described impairment of mucociliary transport in stable allergic asthma or antigen-induced bronchoconstriction is probably not caused by a primary alteration of ciliary function.     

HLA typing used with cultured amniotic and chorionic villus cells for early prenatal diagnosis or parentage testing without one parent's availability

Like fetal fibroblasts and amniotic fluid cells, cultured chorionic villus cells can also be HLA typed with selected typing sera after preincubation with gamma interferon to promote better antigen expression. A modified procedure now in use would also allow any of these cell types to be tested for the presence or absence of all known HLA A,B,C, and DR antigens with standard preplated typing trays. This procedure was used to confirm that an on-going pregnancy had resulted from the successful in vitro fertilization and implantation of an anonymous donor's ovum and could also be of major use in rape or artificial insemination cases when the identity of the possible father(s) is not known.     

Pathologic features of extraosseous Ewing's sarcoma: a report from the Intergroup Rhabdomyosarcoma Study

Eighty-four cases of extraosseous Ewing's sarcoma (EOE) were found during the pathology review of the Intergroup Rhabdomyosarcoma Study I and II. Patients commonly presented during or after adolescence with the most common primary sites including the trunk, extremities, and retroperitoneum. Males were slightly more affected. Histologic sections of 74 tumors in the pathology repository were re-reviewed with attention to rosette formation (positive in 18 cases) and glycogen deposition (++ in 21, + in 36, +/- in 11, and - in 2 of 70 cases examined). Fourteen tumors (7 with rosettes and 7 without) were selected for immunohistochemical and ultrastructural studies, and 13 showed single or multiple neural markers (neuron-specific enolase in 8, S-100 protein in 6, and neurosecretory-type granules in 9). These possible cases of neural EOE could be divided into three subgroups: tumor with bidirectional neuroblastic and schwannian differentiation (5 cases), tumor with monodirectional neuroblastic differentiation (7 cases), and tumor with monodirectional schwannian differentiation (1 case). EOE with a neural nature may be categorized into a spectrum of peripheral primitive neuroectodermal tumors. Clinical, histopathologic, and biologic differences between this disease and conventional sympathetic neuroblastoma are discussed.     

Minimal progesterone support required for the maintenance of pregnancy in mice

A study of the degree of progesterone support required for the maintenance of various stages of pregnancy was undertaken in mice. Mated females were ovariectomized at various stages of pregnancy and progesterone and oestradiol support provided by s.c. Silastic implants with known release characteristics. In the earliest stages of pregnancy (days 1-5), very low concentrations of progesterone (<25% of normal physiological values) were sufficient to maintain pre-implantation stages and allow implantation. In the immediate post-implantation period (days 5-9), the development of implantation sites and decidualization required considerably higher progesterone support. In mid-pregnancy (days 11-14), progesterone alone could not maintain pregnancy unless present in very high amounts; however, the presence of oestradiol during this period lowered the progesterone requirements to well within the physiological range. This effect of oestradiol started on day 11 but required the level of oestradiol support to be kept within strictly defined limits, with high concentrations inducing abortion. Progesterone alone was able to maintain pregnancy from day 15. These results indicate that the minimal progesterone support required for pregnancy in mice varies considerably at different stages of pregnancy and is at least partly modulated by oestradiol.      

Häufigkeit der Hyperlipoproteinämie Typ III bei elektrophoretisch nachweisbarer breiter β-Bande

Zusammenfassung Von 4000 unausgewählten poliklinischen Patienten hatten 395 (10%) eine Hyperlipoproteinämie. 22 Patienten (5,6% der Fälle mit Vermehrungen der Serumlipide, 0,55% der Gesamtpatienten) zeigten elektrophoretisch das Bild einer breiten -Bande. In 2 Fällen (ca. 10% der Patienten, deren Seren in der Agarose-Elektrophorese keine scharfe Trennung der - und Prä--Lipoproteine ergab, 0,25% der Hyperlipoproteinämien) konnte eine Hyperlipoproteinämie Typ III gesichert werden. Bei Beschränkung der Ultrazentrifugation auf Seren mit breiter -Bande werden nicht alle Hyperlipoproteinämien des Typs III erfaßt. Andererseits ist der Anteil des Typs III bei Lipoproteinämiemustern mit unscharfer Trennung von - und Prä--Lipoproteinen (breite -Bande) verhältnismäßig gering.Herrn Prof. Dr. H. H. Bennhold zum 80. Geburtstag gewidmet.     

Receptor-binding function of type 1 pili effects bladder colonization by a clinical isolate of Escherichia coli.

The role of type 1 pili in promoting bladder colonization was examined by constructing two mutant strains of a clinical Escherichia coli isolate. One mutant was isogenic to the parental strain save for a lesion in a gene required for pilus receptor binding; the other mutant was isogenic save for a lesion in the gene encoding the pilus structural subunit. Using mixed infections of the parental and mutant strains in an ascending rat cystitis model, we found that type 1-piliated mutants that lacked the receptor-binding function were as ineffective in bladder colonization as were mutants lacking the entire organelle.     

Chemotherapie mit Cisplatin-Bleomycin und nachfolgende Strahlentherapie bei fortgeschrittenen Kopf-Hals-Tumoren

Summary 42 patients with advanced stage III and IV squamous cell carcinoma of the head and neck were treated with initial cisplatin and bleomycin chemotherapy and subsequent radiotherapy. 39 were evaluable for results, and 3 for toxicity only. 8 patients suffered from stage III and 31 from stage IV tumors, of these 10 with distant metastases. 5 patients underwent later a rescue operation. 27 were previously untreated (= group A) including 2 cases with localized relapses beyond the margins of surgical and/or radiotherapeutic treatment fields. 12 patients had a recurrence within pretreated areas (= group B). The induction chemotherapy alone showed the following results: In group A 4 (15%) CR, 10 (37%) PR, 7 (26%) MR; in group B 3 (25%) PR, 2 (17%) MR. The subsequent radiotherapy mostly consisted of a 65 Gy tumor dose given in 61/2 weeks. The results after completion of the combined modality therapy were: In group A 44% CR, 28% PR; in group B 10% CR and 30% PR. No patient resistant to the initial chemotherapy responded to the radiotherapy. The median survival time of stage III patients was 20 months but only 7 months in stage IV patients. 4 of all live with NED now between 30+ and 41+ months; 1 patient is alive with relapse. All the others are dead after a survival time of max. 32 months, included the 5 with rescue operation. In general, hematologic and renal toxicities were not severe, but nausea and vomiting were the worst tolerated side effects. 1 patient died from septic myocarditis having a WBC nadir of 2000/µl, probably due to additional immunologic deficiency because of inactive liver cirrhosis. The poor results concerning NED survival are discussed. We conclude, that an initial chemotherapy with CDDP and BLM gives good remission effects but its combination with radiotherapy at present fails to produce a NED survival benefit. Further efforts are necessary to improve the CR and the long time survivor rates.

Die Autoren danken folgenden Kollegen für ihre Mitarbeit: Drs. Garbea (HNO), B. Bienko, M. Danker, N. Birke, M. Klessing, K. Lottner, W. Palm