Treatment and prophylaxis of experimental liver metastases of M5076 reticulosarcoma with cis-bis-neodecanoato-trans-R,R-1,2-diaminocyclohexaneplatinum (II) encapsulated in multilamellar vesicles.

cis-Bis-neodecanoato-trans-R,R-1,2-diaminocyclohexaneplatinum++ +-(II) (NDDP) was encapsulated in multilamellar vesicles composed of dimyristoyl phosphatidylcholine and dimyristoyl phosphatidylglycerol at a 7:3 molar ratio. Compared with cisplatin, i.v. administration of an equimolar dose of liposome-encapsulated NDDP (L-NDDP) resulted in 15-fold higher peak platinum levels in the spleen (204.7 versus 13.3 micrograms/g dry tissue), 5-fold higher in the lungs (116.4 versus 21.0 micrograms/g dry tissue), 3-fold higher in the liver (71.6 versus 23.9 micrograms/g dry tissue), and 4-fold higher in the blood (14.8 versus 3.9 micrograms/ml). At the optimal dose and schedule, L-NDDP administered i.p. in mice bearing peritoneal L1210 leukemia resulted in the percentage of median survival time of treated mice divided by median survival time of control mice (%T/C) of 312 versus 225 for cisplatin and free NDDP. When administered i.v., L-NDDP was also more active than cisplatin against L1210 leukemia inoculated i.v. (%T/C 186 versus 142). L-NDDP was markedly active against L1210 leukemia resistant to cisplatin (%T/C, 200 versus 112 for cisplatin). In mice bearing liver metastases of M5076 reticulosarcoma, L-NDDP was significatnly more effective than cisplatin at equimolar doses (mean survival time, 57 +/- 9 (SD) days for L-NDDP versus 42 +/- 3 days for cisplatin, P less than 0.05). L-NDDP was also effective in preventing liver metastases of M5076 when administered up to 24 h prior to tumor inoculation (mean survival, 28 +/- 2 days for L-NDDP versus 22 +/- 2 days for cisplatin, P less than 0.05). L-NDDP is significantly non-cross-resistant with cisplatin and more effective against phagocytic and nonphagocytic murine tumors.

Malignant lymphoma: cardiac involvement at initial presentation.

Malignant lymphoma rarely involves the heart at initial presentation. We have cared for nine cases in the past 8 years. The median age was 45 years (range, 27 to 68). Initial presenting symptoms included chest pain in four, gastrointestinal (GI) symptoms in three, and constitutional "B" symptoms in two. Echocardiography was the most useful noninvasive procedure, and was abnormal in the eight cases studied. Echocardiographic findings included pericardial effusion in six, and mass lesions within the heart in five. Morphologically, the lymphoma was high-grade small noncleaved in four, immunoblastic sarcoma in one, and diffuse large-cell type in four. Clinical staging workup revealed widely disseminated disease in seven. In spite of multiagent chemotherapy, survival was short (median, 1.5 months). Interestingly, four of these patients were homosexual or bisexual men, who fulfill the criteria for acquired immune deficiency syndrome (AIDS).

Long-term results of the APO protocol (vincristine, doxorubicin [adriamycin], and prednisone) for treatment of mediastinal lymphoblastic lymphoma.

Twenty-one patients with biopsy-proven mediastinal lymphoblastic lymphoma were treated with the APO protocol (vincristine, doxorubicin, and prednisone). Treatment consisted of two years of therapy with a modified doxorubicin-containing acute lymphoblastic leukemia regimen with preventive cranial irradiation and intrathecal methotrexate. The median age in the group was 13 years (range, 2.5-22 years). Complete remission was obtained in 20 of 21 patients. Three patients required mediastinal irradiation for successful remission induction. Six patients have subsequently relapsed: two in the central nervous system, one in the central nervous system and testicle, one in the testicle, one in the pleura, and one in the abdomen. The median follow-up is six years (range, 16 months to 9.5 years) and a Kaplan-Meier estimate of disease-free survival at three years is 58% +/- 23% (2 SE).

Development of lymphosarcoma lines with high metastatic ability to lymph nodes and visceral organs in BALB/c mice.

A metastatic tumor population was isolated in BALB/c mice during routine s.c. passage of the colon 26 adenocarcinoma. The tumor metastasized to lymph nodes, liver, spleen, ovary and kidney. A primary culture established from the s.c. growing tumor was composed of both adherent and nonadherent cells. These two cell types were successfully separated from the primary culture and designated CMS (suspension cells) and CMA (adherent cells). The CMS and CMA cell lines are morphologically distinct in culture; however both formed similar histopathologic tumors when inoculated s.c. Furthermore, both tumor lines showed identical metastatic patterns in BALB/c mice with involvement of lymph node, liver, spleen, ovary and kidney. CMS and CMA expressed T-antigen as revealed by FITC-labeled-anti-Thy 1.2 antibody. Chromosome analysis and morphologic studies by light and electron microscopy indicated that the present metastatic lines have no relationship with the colon 26 adenocarcinoma and seem to be non-thymic T-cell lymphosarcomas which developed spontaneously in BALB/c mice.

In vivo and in vitro properties of malignant variants of RAW117 metastatic murine lymphoma/lymphosarcoma.

Using the RAW117 lymphoma/lymphosarcoma system syngeneic to Balb/c strain mice, variant sublines have been selected for enhanced blood-borne liver colonization in vivo or for lack of binding to immobilized lectins in vitro. The kinetic organ distributions of intravenously injected, 3H-thymidine-labelled RAW117 parental cells and a subline sequentially selected ten times for enhanced liver colonization were similar, suggesting that the differences in malignancy between these two cell lines were not due to dramatic differences in organ localization properties. Examination of the malignant properties of the selected sublines and cell clones derived from these in immune-impaired animals indicated that host immune status was important in determining the quantity of experimental metastases in this system. Although impairment of T-cell or NK-mediated anti-tumor responses by using 400 R 60Co-irradiated or Balb/c nude (nu/nu) mice suggested that certain immunologic responses were not effective in preventing experimental metastasis, impairment of macrophage function with chlorine, silica, trypan blue, carrageenan, cyclophosphamide or pristane were effective and resulted in enhanced malignancy of the parental RAW117 line. In contrast, impairment of macrophage function had little or no effect on the experimental metastatic properties of highly malignant RAW117 sublines or clones. In vitro humoral responses or cell-mediated immunologic assays using lymphoid cells from normal or tumor-bearing hosts failed to demonstrate antibody-mediated or antibody-dependent cell-mediated cytotoxicity (ADCC), T-cell or NK-cell responses against RAW117 cells. However, poly I: C activated macrophages were more effective against parental RAW117 cells than against a highly metastatic subline in cytolysis and cytostasis assays suggesting that the highly metastatic RAW117 cells can more readily escape macrophage-mediated host defenses.

Central nervous system metastases from non-Hodgkin's lymphoma: treatment and prophylaxis.

Central nervous system (CNS) lymphoma was identified in 96 patients treated for non-Hodgkin's lymphoma at Memorial Sloan-Kettering Cancer Center between 1975 and 1981. During the same period, 68 other patients with non-Hodgkin's lymphoma but no CNS disease received prophylactic CNS chemotherapy. In the 156 total patients, the lymphomas were diffuse in 96 percent, and 67 percent were stage IV at diagnosis. CNS involvement was present at initial diagnosis in 27 percent, at relapse in 26 percent, and during the course of progressive systemic disease in 47 percent. CNS involvement was asymptomatic in 10 percent. Cytologic study of the cerebrospinal fluid was the most sensitive and specific laboratory test, but often (22 percent) more than one lumbar puncture was required to identify malignant cells. CNS lymphoma was treated in 85 patients, 46 by intracerebroventricular cannulae; 81 percent improved. Although median survival after the diagnosis of CNS disease was four months, there were seven long-term disease-free survivors and the CNS disease contributed to death in only 14 percent. In 52 percent of treated patients, there was no CNS lymphoma at autopsy. CNS prophylaxis was with methotrexate or cytosine arabinoside, usually by lumbar puncture; an intraventricular cannula was used in seven patients. Although this group of high-risk patients with non-Hodgkin's lymphoma had a high systemic response rate and the median projected survival was greater than five years, CNS lymphoma developed in eight patients (12 percent). In five, CNS lymphoma occurred as an apparently isolated relapse site. The role of CNS chemoprophylaxis in high-risk patients with non-Hodgkin's lymphoma is still uncertain.

Isolation and characterization of cortisol-sensitive and -resistant P1798 mouse lymphosarcoma cell lines.

Three cell lines have been isolated and characterized from the P1798 mouse lymphosarcoma. One line, derived from a glucocorticoid-resistant tumor, was glucocorticoid-resistant in vitro. The other two cell lines, derived from glucocorticoid-sensitive and -resistant parental tumors, respectively, were shown to be glucocorticoid-sensitive in vitro. The glucocorticoid receptor from all three cell lines bound glucocorticoid with similar affinity and capacity. However, based on Sephacryl S-300 gel filtration, the glucocorticoid receptor from the resistant cell line was smaller than that of the two sensitive cell lines. Moreover, the glucocorticoid receptor from the resistant cell line accumulated to a greater extent in the nucleus. This resistant cell line thus resembles the nti variant of the S49 lymphoma cell line. All three cell lines were tumorigenic and metastatic when reimplanted into mice, contained the normal mouse diploid complement of 40 chromosomes and exhibited the same responsiveness to cortisol in vivo as they did in vitro. It is concluded that the ready passage of these cell lines in vitro or in vivo and the presence of the small receptor in the resistant line should make them excellent model systems for the study of glucocorticoid resistance.

Primary reticulum-cell sarcoma (microglioma) of the brain with massive cardiac metastasis. Case report.

A patient is presented with reticulum-cell sarcoma of the brain and a large metastasis to the heart.

[Skeletal involvement in malignant lymphoma]. / Der Skelettbefall bei malignen Lymphomen.

Of 114 patients with Hodgkin's disease reviewed, 13 (11%) had bone involvement. The typical osseous lesion in Hodgkin's disease is a secondary manifestation in the axial skeleton. The lesions are mainly lytic; there is no relation between the site of the affection and the character of the lesion. Of 261 patients with non-Hodgkin lymphoma, 19 (7.3%) had bone involvement. Non-Hodgkin lymphoma very rarely affects the bone primarily; these lesions are lytic. Involvement of the appendicular skeleton is reported to by typical; this cannot be confirmed by our study. Most secondary osseous lesions in non-Hodgkin lymphoma are found in the cranium, the spine and the sternum; this pattern of distribution as well as the mainly lytic appearance can be considered typical.

Diagnosis of leptomeningeal metastasis.

Forty-one cases of leptomeningeal metastases from solid and hematological tumours were studied clinically and pathologically. Neurological symptoms and signs, cerebrospinal fluid characteristics and radiographic appearance were reviewed. The role of the biochemical markers, computer tomography scans of the brain and myelography in the diagnosis of patients with leptomeningeal metastasis were determined. The subject of the study was an investigation of the value of various diagnostic procedures to increase the accuracy of the diagnosis leptomeningeal metastasis.

T-immunoblastic lymphoma mimicking B-immunoblastic lymphoma.

A T-cell immunoblastic lymphoma having plasmacytoid features that mimic B-cell immunoblastic lymphoma, is described. The lesion was composed of sheets of pleomorphic plasmacytoid cells that displayed a helper T-cell immunophenotype (Leu-1+, Leu-3+, Leu-4+, Leu-5+, Leu-9-, Leu-2-). Ultrastructural features were consistent with a T-cell lymphoma. Flow cytometric analysis revealed that the cells were DNA triploid and had a high proliferative activity. Although the histology of immunoblastic lymphomas alone may suggest either a T- or B-cell phenotype, immunophenotyping is essential in making this distinction.

[Action of doxorubicin and a doxorubicin-heparin complex on the growth and metastasis of experimental tumors and the hemostatic system indices]. / Deistvie doksorubitsina i kompleksa doksorubitsin--geparin na rost i metastazirovanie éksperimental'nykh opukholei i nekotorye pokazateli sistemy gemostaza.

The electrophoretic and spectral analyses have been used to show the possibility to form a complex consisting of doxorubicin and adriamycin with heparin, the molar ratio being 6:1 and pH 4.8-7.4. Doxorubicin and adriamycin had procoagulant properties but the doxorubicin-heparin complex showed an anticoagulant activity. In experiments on rats with the Pliss lymphosarcoma and sarcoma 45 the doxorubicin-heparin complex depressed more efficiently the tumour growth and metastasis spreading. The combination of doxorubicin and the doxorubicin heparin complex with the trypsin-heparin complex which imitate the hyperfunction of anticoagulative system markedly increased the antitumour effects.

Discrete peritoneal and pericardial implants of non-Hodgkin lymphoma--CT findings and review of the literature.

Peritoneal spread of non-Hodgkin lymphoma is rare: fewer than three percent of persons afflicted with this disease develop peritoneal spread. Pericardial involvement by non-Hodgkin lymphoma is equally rare. We report an instance of peritoneal and pericardial spread in a patient with non-Hodgkin lymphoma that was detected only by CT scan. The peritoneal lesions were not visible by ultrasound examination. A pertinent review of the literature is presented.

Neurologic diseases associated with lymphosarcoma in ten dogs.

Lymphosarcoma was diagnosed in 10 dogs with initial signs referable to the nervous system. Six dogs had signs of spinal cord disease, 2 had signs of peripheral nerve disease, and 2 had signs of cranial disease. The diagnosis of lymphosarcoma involving ther nervous system was made prior to the death of each dog, and necropsy confirmed the clinical diagnosis in each case. The clinical diagnosis was based on the results of blood analysis, bone marrow examination, lymph node cytology, cerebrospinal fluid evaluation, and tumor biopsy.

Lymphosarcoma and associated immune-mediated hemolytic anemia and thrombocytopenia in horses.

Three horses with equine lymphosarcoma were examined because of clinical signs including chronic weight loss, respiratory distress, peripheral edema, and chronic colic. Clinicopathologic findings included evidence of an immune-mediated hemolytic anemia. Immune-mediated thrombocytopenia also was diagnosed in 1 of the horses and suspected in another. One horse died in spite of treatment, 1 died 5 hours after surgical removal of a tumor encircling the jejunum, and 1 was euthanatized because of deteriorating condition. Necropsy of each horse revealed extensive neoplastic infiltration of peripheral lymph nodes and abdominal or thoracic viscera with neoplastic lymphocytes.

[Cardiac involvement in 2 cases of malignant non-Hodgkin's lymphoma. Course of cardiac involvement under chemotherapy]. / Atteinte cardiaque dans deux cas de lymphomes malins non hodgkiniens. Evolution de l'atteinte cardiaque sous chimiothérapie.

In a recently published post-mortem series the incidence of cardiac lesions in malignant lymphoma was estimated at about 8.7%. These lesions rarely produce specific cardiac symptoms; they usually are late manifestations of a disease with multiple secondary lesions or are discovered at autopsy. In most patients the lesions are not limited to the heart but represent the extension to that organ of a malignant lymphoma. We observed two cases of cardiac lesions secondary to malignant non-Hodgkin lymphoma and we were able to evaluate their response to chemotherapy. In the first patient the cardiac symptoms revealed the lymphoma; in the second patient the cardiac involvement was discovered 4 years after the lymphoma was diagnosed. In both cases the cardiac lesions were detected by two-dimensional echocardiography. They presented as polypoid masses filling the right atrium and associated with periaortic thickening in the first case, and as a large heterogeneous mass including a tricuspid valve leaflet and extending to the free wall of the right ventricle in the second case. Pericardial effusion was present in the two patients. These echocardiographic findings were confirmed computerized tomography and catheterization. In the first case, followed up for one year, the echocardiographic images reverted to normality after chemotherapy. The second patient, unfortunately, did not respond to chemotherapy and deteriorated rapidly.

Cancer of unknown primary site. Deciding how far to carry evaluation.

Management of most patients who present with metastatic cancer from an unknown primary site is challenging. These patients often are debilitated from the onset of their disease, have symptoms that are hard to control, and respond poorly to systemic therapy. The decision regarding the extent of a frequently unrewarding diagnostic evaluation, especially in these days of cost containment, is difficult. Knowing that few will benefit from aggressive therapy, the treating physician should make quality of life the most important goal in caring for these patients.

[Metastatic cancer of the heart--a clinicopathologic study of 68 cases].

The study of 68 autopsy cases of metastatic cancer of the heart is reported. There were 41 male and 27 female. The age was from 26-89 years. The primary neoplasms are as follows: carcinoma of lung (26.5%), lymphosarcoma (14.7%), leukemia (11.8%), malignant melanoma (8.8%), carcinoma of breast (7.4%) and of kidney (7.4%). The laterality ratio of the heart was; right: left is 1:2. The myocardium was involved in 50 cases, the pericardium, 30 cases and the endocardium, 16 cases. 19 cases (27.9%) had symptoms referable to the metastatic disease in the heart. None of the patient was correctly diagnosed before death as to the metastatic lesion in the heart. 88.2% (60/68) of cases died of general metastases, in which 14 succumbed directly from metastatic cancer of the heart.

[Cerebral localizations of non-Hodgkin's malignant lymphoma. Contribution of x-ray computed tomography]. / Localisations cérébrales des lymphomes malins non hodgkiniens. Apport de la tomodensitométrie.

At the present time, CT scan imaging occupies an essential place in the diagnostic approach and course of cerebral non-Hodgkin's malignant lymphoma. Results of CT scan investigations are reported in 17 patients, 8 with primary and 9 with secondary lymphoma. The lesions observed, hypo-, iso- or faintly hyper-dense, took-up contrast almost constantly in an intense and well limited homogeneous manner. The subependymal infiltration noted was suggestive of the disease particularly since it was often associated with a paraventricular localization in the white substance, corpus callosum or central gray nuclei. However, no correlation existed with the primary or secondary nature or histologic type of lymphoma, and histopathologic confirmation was necessary from surgical biopsy specimen. Appearances of primary and secondary lymphoma are superimposable, apart from certain cases with co-existing secondary lymphoma and bone lysis or a contiguous endocranial tumor. Follow-up CT scan imaging confirms clinical remission, or recurrence raising the problem of radionecrosis.

[Bronchial localization of a T-cell immunoblastic lymphoma. Transformation from mycosis fungoides]. / Localisation bronchique d'un lymphome immunoblastique T. Transformation d'un mycosis fongoïde.

A case report is presented of a patient with a pleural effusion subsequently shown to have a localised immunoblastic lymphoma of the bronchus of non-Hodgkin's type. The development of this lymphoma in a patient with mycosis fungoides underlines the potential for the transformation of a T cell epidermoid lymphoma of low grade malignancy to a lymphoma of high grade malignancy.