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Prevention of bacterial infection in neutropenic patients with hematologic malignancies. A randomized, multicenter trial comparing norfloxacin with ciprofloxacin. The GIMEMA Infection Program. Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto.

OBJECTIVE: To compare the efficacy of norfloxacin and ciprofloxacin in preventing bacterial infection in neutropenic patients. DESIGN: A randomized, controlled, multicenter trial. SETTING: Twenty-one hematologic units in tertiary care or university hospitals. PATIENTS: Eight hundred and one consecutive, afebrile, adult patients who had hematologic malignancies or who had bone marrow transplantation and chemotherapy-induced neutropenia (neutrophil count, less than 1000/mm3) expected to last more than 10 days. INTERVENTION: Patients were randomly assigned to receive orally every 12 hours norfloxacin, 400 mg, or ciprofloxacin, 500 mg. MEASUREMENTS: Efficacy analysis was done for 619 patients: 319 treated with norfloxacin and 300 treated with ciprofloxacin. MAIN RESULTS: More patients receiving ciprofloxacin did not develop fever during neutropenia and did not receive antibiotics (34%) compared with those receiving norfloxacin (25%) (P = 0.01). Patients receiving ciprofloxacin had a lower rate of microbiologically documented infection (17% compared with 24%; P = 0.058), particularly of infection from gram-negative bacilli (4% compared with 9%; P = 0.03). The interval to the first febrile episode was also longer in patients receiving ciprofloxacin (8.3 compared with 7.2 days; P = 0.055). The rates of clinically documented infection, fever of unknown origin, and mortality as well as compliance and tolerability were similar in the two groups. Patients who had neutropenia for less than 15 days, who had severe neutropenia for less than 7 days, and who received antifungal prophylaxis benefited most from ciprofloxacin therapy. CONCLUSION: Ciprofloxacin should be used to prevent the development of infection in neutropenic patients with hematologic malignancies.

Adolescent↗

[Studies on mechanism of carcinogenesis in vitro. IV. Studies on relationship between frequency of chromosome 15 monosomy and malignant expression of different clones from malignantly transformed baby hamster lung cells (BHL B4)].

The proceeding of malignantly transformed rodent cells in vitro is often accompanied by regular variation of chromosome numbers and structures. In order to clarify the relationship between them, we obtained five clones C1-1-5-from BHL B4, cell line, and analysed their biological characteristics. Results showed a positive correlation between frequency of chromosome 15 monosomy, it is suggested that suppressive gene of malignant phenotype be located on chromosome 15.

Animals↗

Malignant melanoma simulants arising in congenital melanocytic nevi do not show experimental evidence for a malignant phenotype.

Proliferative neoplasms that resemble malignant melanoma may develop in large congenital melanocytic nevi, prenatally or in the neonatal period, although these lesions rarely show the progressive growth or behavioral characteristics of melanoma. This report describes the genetic, biologic, and immunologic characteristics of six tissue culture cell lines derived from two neoplasms present in congenital melanocytic nevi in two newborn infants. Both neoplasms had clinical and histologic features of malignant melanoma. Despite these features, cells from all lines were phenotypically benign, as evidenced by a normal karyotype, their expression pattern of pigment cell-associated antigens, absence of melanoma-associated ganglioside GD2, their mitogenic response to the tumor-promoting phorbol ester 12-0-tetradecanoyl phorbol-13-myristate, their inability to grow anchorage independently in soft agar, and prolonged but finite life span. The cells did not produce tumors in nude mice, but they remained viable at the injection site for over 7 months.

Antibodies, Monoclonal↗

Characterization of tumor cells in malignant fibrous histiocytomas and other soft-tissue tumors, in comparison with malignant histiocytes. II. Immunoperoxidase study on cryostat sections.

The authors have investigated a possible relationship between tumor cells of malignant fibrous histiocytomas (MFHs) and histiocytes. This relationship was studied by means of immunophenotyping using monoclonal antibodies specific for the monocyte cell lineage (FMC-17, Mac-1, OKM-1, Leu-M1, and lysozyme) and mono- and polyclonal antibodies specific for fibroblasts (respectively, FIB-86 and FSG). The immunophenotypes of the MFH tumor cells were compared with those of tumor cells of "true" histiocytic tumors. Monocyte lineage-specific determinants could be demonstrated in varying amounts on cells of the "true" histiocytic tumors but not on cells of MFH or other soft-tissue tumors. The reverse was true for determinants on fibroblasts. The absence of these determinants on malignant histiocytes, and their presence on MFH (and also on benign fibrous histiocytomas, fibrosarcomas, schwannomas, osteosarcomas, hemangiosarcomas, leio- and rhabdomyosarcomas) supported the conclusion that MFH tumor cells originate from mesenchymal cells which do not belong to the mononuclear phagocytic system. Subdivision of the MFH tumors revealed that the storiform-pleomorphic subtypes could express HLA-Dr/Ia antigens, like histiocytic tumors. The inflammatory cell subtype, however, lacked these antigens.

Adult↗

[Diagnostic value of determining alpha1 protease inhibitor and alpha2 macroglobulin in the serum of women with malignant and non-malignant ovarian tumors and uterine myomas].

In the serum of 21 women with malignant ovarian tumours, 13 with uterine myomas and 16 with cysts the concentrations were determined of alpha 1 inhibitor of proteases and alpha 2 macroglobulin by immunodiffusion, and the functional activity of both inhibitors which made possible calculation of the specific activity (units of inhibitory activity per one gram of inhibitor protein). In women with malignant tumours the specific activity of alpha 1 inhibitor was decreased, suggesting that a part of the inhibitor was functionally inactive. This decrease was statistically significant in relation to the control group and the groups of myomas and cysts, but was independent of the degree of disease progression. The specific activity of alpha 2 macroglobulin was significantly decreased only in patients with grade IV degrees of clinical progression (according to FIGO) in relation to the control group and to the group with cysts.

Adolescent↗

[A case of synchronous double primary malignant neoplasms (malignant astrocytoma, and lung cancer) diagnosed by autopsy].

Discussed is a deceased patient, a 54-year-old male, who was admitted to hospital with the chief complaint of motor aphasia. Computed assisted tomography in the cranium showed a massive lesion in the left brain. Further, chest X-ray showed an abnormal tumorous shadow with a pleural indentation in the left middle lung field. In spite of a negativity of cancer cells in a bronchial biopsy and a brushing, we decided that this case reflected a lung cancer with brain metastasis. However, on autopsy, the tumor in the lung histologically was determined as being an (adenocarcinoma alveolar cell type) and the brain tumor was found to be a malignant astrocytoma. We have reported on this case because a double primary neoplasm, a malignant astrocytoma and lung cancer, is rare in the literature.

Adenocarcinoma, Bronchiolo-Alveolar↗

Malignant fibrous histiocytoma and malignant melanoma: the role of immunohistochemistry and electron microscopy in the differential diagnosis.

Malignant fibrous histiocytoma (MFH) and malignant melanoma (MM) occur together often in the differential diagnosis of poorly differentiated neoplasms. They differ, however, in their biologic behavior and recommended treatment. Investigators have therefore explored a variety of special techniques, including electron microscopy (EM) and immunoperoxidase (IP), to classify these tumors accurately and to separate them from each other. To determine the usefulness of IP and EM in the classification of these tumors, we applied a Fontana-Masson stain and IP probes for vimentin, alpha-1-antitrypsin (alpha-1-A), human melanoma black (HMB)-45, and S-100 protein to twelve MMs and nine MFHs, all of which had available EM studies. Three of twelve MMs were amelanotic. All tumors contained vimentin. Eight of twelve MMs and six of nine MFHs contained alpha-1-A. Ten of twelve MMs and no MFHs contained HMB-45. Eleven of twelve MMs and, surprisingly, two of nine tumors classified by light and EM as MFHs contained S-100 protein. When problems arose with either IP negativity or potentially misleading cross-reactivity, careful EM study allowed definitive classification.

Adult↗

[Intravascular malignant lymphoma (malignant angioendotheliomatosis). Apropos of a case with histologic, immunohistochemical and ultrastructural studies].

We report a new case of intravascular malignant lymphoma that arose in an 81-year-old woman. The most prominent symptoms were impressive dermatologic anomalies including painful, diffuse edema over which arborescent telengiectasic lesions could be seen. This clinical picture was associated with the presence, in deep skin biopsy specimens, of mononucleate tumor cells located within the lumen of dermal vessels. Complementary immunohistochemical and ultrastructural studies confirmed that the intravascular tumor growth was lymphomatous in nature. Clinical manifestations of this disease are recalled, and histopathologic features as well as the characteristic location of this malignant lymphoma are analyzed and discussed. Thus, we agree with Félix [3] and Witschi [6] that the cords of cells that will give rise to the follicular cells surrounding the ovocytes originate only from the coelomic epithelium; the primary mesenchyma forms the cortical stroma, and this embryonic type tissue, characterized by enourmous physiologic plasticity, differentiates into endocrine tissue to form the inner theca. the mesonephros plays no part whatsoever in the formation of the ovary.

Aged↗

[Triple malignancy including bladder carcinoma, prostate carcinoma and malignant lymphoma: a case report].

A 70-year-old man was admitted to our hospital with the complaint of lower abdominal mass. Previously, he had received partial cystectomy and radiation of 38 Gy for bladder transitional cell carcinoma and transurethral resection of prostate and diethylstilbestrol administration for prostatic adenocarcinoma. The third tumor was located between the bladder and lower abdominal wall with inguinal lymph node swelling. Biopsy specimen revealed malignant lymphoma. After 2 courses of combination chemotherapy consisting of vincristine, prednisolone and procarbazine, complete remission was achieved. We discuss about multiple malignancies including urological organs.

Adenocarcinoma↗

[Malignant neoplasms and potentially malignant hyperplasia in children and adolescents from material at the Department of Pathomorphology, Institute of Mother and Child during 1978/79-1983].

531 cases of malignant neoplasms and potentially malignant hyperplasia in children and adolescents diagnosed in the Department of Pathomorphology, Institute of Mother and Child between 1978/79 and 1983 are presented. Only patients treated in this hospital were included into the study. The most common diagnoses were neuroblastoma (68 cases), rhabdomyosarcoma (62 cases), nephroblastoma (56 cases), osteogenic sarcoma (47 cases), non-Hodgkin lymphoma (41 cases). Besides neoplasms most typical for childhood and adolescence the rare less typical cases were also seen.

Adolescent↗

[Anemia in malignant tumor diseases. I. Tumor-induced loss of transferrin and its relation to tumor size and degree of malignancy in the rat model].

Cellular uptake of 67Ga-labelled transferrin by the tumor tissue was studied in rats with tumors of different malignancy and different tumor mass using the slowly growing Morris hepatoma 5123C, the moderately growing Novikoff hepatoma and the very fast and aggressive Yoshida hepatoma AH130. The cellular accumulation of 67Ga-transferrin was found to correlate with the proliferation activity of the tumor. The 67Ga-transferrin concentration in the very fast growing Yoshida hepatoma was 4.8 times higher than the concentration in the slowly growing Morris hepatoma. The uptake of 67Ga-transferrin by the tumors resulted in a faster disappearance of circulating 67Ga-transferrin from the blood. The rate of disappearance correlated with the proliferation activity and the spread of the tumors. Using tumors of identical size the elimination of 67Ga-transferrin from the blood was much faster in the rats with Yoshida hepatoma than in those with the slowly growing Morris hepatoma. On the other hand, using tumors of different tumor size it could be demonstrated that the rate of disappearance of 67Ga-transferrin from the blood correlated directly with tumor mass. It is concluded that cellular incorporation of transferrin within the tumor cells results in a loss of circulating transferrin, which correlates with tumor mass and proliferation of tumor. This mechanism is supposed to be the cause for the hypotransferrinemia seen in patients with malignant tumors.

Anemia↗

[Triple primary malignancies (malignant melanoma, laryngeal cancer and hepatoma)].

A 61 year-old male patient, diagnosed to have a malignant melanoma in the left arm in April, 1981, was treated by chemotherapy (gamma-INF and DAVP) and a left axillary lymphadenectomy. In March, 1985, he had complained of hoarseness and an early laryngeal squamous cell carcinoma was found, and was subjected to laser treatment. On May 25, 1986, during his hospitalization for treatment of a multiple metastasis of a malignant melanoma, he suddenly suffered from a gastroduodenal perforation. During an emergency operation, a third cancer, a primary mixed hepatocellular and cholangiocellular carcinoma, was discovered.

Carcinoma, Hepatocellular↗

[A frequent malignant tumor of the soft tissues, malignant fibrohistiocytoma. Current interest: apropos of 2 cases disclosed by vascular complications].

Malignant fibrohistiocytoma represents one of the most common malignant tumors of soft tissues. Previously difficult to diagnose with precision, it can now be detected pathologically as a result of recent techniques for investigating cellular development. Treatment is by wide exeresis, prognosis remaining reserved and requiring prolonged postoperative surveillance.

Adult↗

[Immunologic properties of malignant and non-malignant L cell sublines. II. Immunogenicity, sensitivity to complement and T-lymphocytes, cell secretions modifying immune reactions].

The malignant subline of L cells did not differ from the initial benign subline in such immunological parameters as immunogenicity, ability for modigying immunological reactions by their metabolic products, sensitivity to the lyzing action of the complement, ability for surface adsorption of lymphocytes. The cells of the malignant subline were somewhat less sensitive to the lyzing action of T lymphocytes than the cells of the initial subline.

Animals↗

[A phase II study of mitoxantrone in refractory and relapsed malignant lymphomas. Cooperative Study Group of Mitoxantrone in Malignant Lymphomas].

A phase II clinical trial of mitoxantrone in refractory or relapsed malignant lymphomas was conducted by a cooperative study involving 17 institutions. Of 46 patients entered, 33 were evaluable for responses and toxicity. Thirty-one of the 33 had been previously exposed to adriamycin at a median dose of 220 mg/m2 (range 21-489 mg/m2), and two additional patients had each been given THP-adriamycin at a dose of 80 mg/m2 or 4'-epi adriamycin at a dose of 69 mg/m2. Mitoxantrone was administered in 3 different schedules: 8-12 mg/m2, every 3-4 weeks in 23 patients; 4-6 mg/m2, weekly, in 3 patients; and 2-4 mg/m2, for 5 days, in 7 patients. Summarizing the responses obtained in the 3 schedules, there were 2 partial responders among 5 with Hodgkin's disease, while there were 8 complete responders and 4 partial responders among 28 with non-Hodgkin's lymphoma. The overall response rate for all the evaluable patients was 42% with a complete response rate of 24%. The median response duration was 7+ weeks (range 4-27+ weeks) for complete responders and 7 weeks (range 4-46+ weeks) for partial responders. The major toxicity was myelosuppression: leukocytopenia less than 3,000/microliter occurred in 79% of patients, and thrombocytopenia less than 75,000/microliter in 35%. Other toxic effects were minimal, mild nausea and/or vomiting occurred in 39%, and diarrhea in 3%. Possible drug-related liver and renal dysfunctions were observed in 19% and 10%, respectively. The favorable response to mitoxantrone in patients with prior anthracycline antibiotic therapy suggests that the drug is not fully cross-resistant with anthracycline antibiotics, and that this drug is of value in combination with other drugs as a salvage therapy for patients with refractory or relapsed malignant lymphomas.

Adolescent↗

[Manifestation of a malignant lymphoma of high grade malignancy in the terminal stage of mycosis fungoides. Enzyme-cytochemical and immunocytological investigations (author's transl)].

Report on a patient with mycosis fungoides, in whom after a long course the disease developed rapidly into a malignant lymphoma of high grade malignancy. The diagnosis was confirmed by cytomorphological and enzyme-cytochemical methods (demonstration of hydrolytic enzymes in cryostat sections, cutaneous smears and cell suspensions extracted from skin lesions), as well as by immunocytological methods (differentiation of lymphocyte sub-populations). In the tumour stage of mycosis fungoides, a polymorphous infiltrate composed of lymphocytoid and monocytoid cells prevailed, while a proliferation of lymphoblastic cells was present in the terminal stage of the disease. These cells showed no longer the properties of mature lymphocytes and differed also in their enzyme-cytochemical pattern.

Histocytochemistry↗

[Phase III study of bestatin in patients with malignant skin tumors. (1) Malignant melanoma].

As a co-operative study involving 18 medical research institutions, we have made a randomized, controlled study (phase III study) of Bestatin in the treatment of malignant melanoma (stage Ib, II) over the last 4 years. The results were as follows; Bestatin significantly prolonged disease-free intervals by 9-20 month. Bestatin significantly prolonged survival periods by 10-16 months. Side effects of Bestatin, chiefly comprising of reversible gastro-intestinal disturbances, were observed in 7.1% of Bestatin-treated cases. These findings suggest that Bestatin is a very useful agent for treating for stage Ib and II malignant melanomas.

Adult↗

[Phase II study of NK 171 (etoposide) on malignant lymphomas and acute leukemia. A cooperative study group on NK 171 in hematological malignancies].

A Phase II clinical trial of NK 171 (Etoposide), a semisynthetic podophyllotoxin, was undertaken in 56 patients with advanced malignant lymphoma and 36 patients with acute leukemia. The dosage of NK 171 was 110-130 mg/m2 day p.o. or 80-100 mg/m2 day i.v. for 5 consecutive days. Of the 92 patients, 23.9% obtained a complete or partial remission. By tumor type, good responses were obtained in non-Hodgkin's lymphoma (34%, 17/50), Hodgkin's disease (25%, 1/4), AML (21.4%, 3/14), and CML-BC (25%, 1/4). Side effects included leukopenia (78.4%), alopecia (62.0%), anorexia (40.2%), nausea (30.4%) thrombocytopenia (25.6%) and fever (16.3%). These results demonstrated NK 171 to be an effective agent against malignant lymphoma and acute myeloblastic leukemia.

Acute Disease↗