Treated thymic lymphoma: comparison of MR imaging with CT.

PURPOSE: To determine the appearance of treated thymic lymphoma at magnetic resonance (MR) imaging and to compare the results with findings from posttherapy computed tomography (CT) and clinical outcome. MATERIALS AND METHODS: MR images and CT scans in 25 patients with thymic lymphoma were reviewed. Dimensions of residual masses on MR and CT images were compared. Signal intensity on MR images was assigned to four patterns: (a) low heterogeneous, (b) low homogeneous, (c) high heterogeneous, and (d) high homogeneous. The presence of cysts, calcification, and fatty infiltration was noted. Abnormality of intrathoracic nodes was also documented. RESULTS: Dimensions of residual thymic masses were greater on MR images than on CT scans. The signal intensity pattern was low homogeneous or heterogeneous in 19 patients. Two of these patients had relapse within 1 year. High heterogeneous signal intensity was observed in five patients, four of whom had relapse. Cysts were seen at MR imaging in six patients, of whom one had relapse, but were seen in only one patient at CT. CONCLUSION: Treated thymic lymphoma usually has low signal intensity on MR images regardless of residual mass size, and cysts of high signal intensity may be seen. Relapse occurred mainly in large-volume masses or masses of high heterogeneous signal intensity, indicating that close follow-up or biopsy should be considered in such cases.

Dexamethasone, cyclophosphamide, idarubicin and etoposide (DC-IE): a novel, intensive induction chemotherapy regimen for patients with high-risk multiple myeloma.

We evaluated toxicities and responses to a novel, dose intensive and time sequenced, chemotherapy programme (DC-IE) in 45 patients with high-risk myeloma. DC-IE consisted of: dexamethasone (days 1-4); cyclophosphamide (day 5); idarubicin and etoposide (days 8-10). Complete response (CR) was achieved in four patients, six patients achieved near complete responses (nCR) and 21 patients achieved a partial remission (PR). Overall response rate was 76% (CI 56-94%) for newly diagnosed patients (n = 21) and 62% (CI 36-81%) for relapsed/refractory patients (n = 24). Toxicities were limited to myelosuppression; two patients died of sepsis during neutropenia (4%). DC-IE is active and tolerable for high-risk multiple myeloma, including patients with relapsed or refractory disease to anthracycline containing regimens.

Deoxycoformycin (pentostatin): clinical pharmacology, role in the chemotherapy of cancer, and use in other diseases.

Pentostatin (2'-deoxycoformycin, dCF) is a purine nucleoside analog and a product of the fermentation of Streptomyces antibioticus. It is a tight-binding inhibitor of adenosine deaminase (ADA), an enzyme essential in the cellular metabolism of purines. Children with congenital absence of ADA suffer from atrophy of lymphoid tissues and severe combined immune deficiency (SCID) syndrome. It was hypothesized that pentostatin would be lymphocytotoxic and this proved to be true; this finding prompted its investigation in lymphoid neoplasms. It was anticipated that pentostatin would be most active in neoplasms with high intracellular concentrations of ADA, e.g. acute lymphocytic leukemia (ALL), particularly of the T-cell variety. Although pentostatin proved to be active in ALL, large doses were required and major toxic effects outweighed therapeutic benefits. By contrast, pentostatin proved to be exceptionally active in hairy cell leukemia (HCL), a B-cell neoplasm with low intracellular concentrations of ADA. Pentostatin has since been shown to possess activity in chronic lymphocytic leukemia, prolymphocytic leukemia, cutaneous T-cell lymphomas, adult T-cell lymphoma-leukemia, and low grade non-Hodgkin's lymphomas. It potentiates the activity of vidarabine against viruses and against the cells of acute myeloid leukemia. Pentostatin is inactive in melanoma and renal carcinoma, but has not been adequately evaluated in other solid tumors. The toxic effects of pentostatin include renal failure, central nervous system (CNS) depression, immunosuppresion, keratoconjunctivitis, and opportunistic infections. In the absence of pre-existing bone marrow compromise, pentostatin produces only mild myelosuppression. Aside from its use as an antineoplastic agent, pentostatin has potential applications as an immunosuppressive drug, as an antiviral agent, as an antimalarial compound, and in the protection of cells of the CNS from damage induced by ischemia and anoxia. Clinical studies with pentostatin are ongoing, and its roles in the management of neoplastic and non-neoplastic diseases have yet to be fully defined.

Clinical manifestations of chronic granulocytic leukemia.

CGL is a highly specific disease that is defined by strict hematologic parameters that include a pathognomonic differential leukocyte count. Usually CGL is accompanied by the presence, in bone marrow cells, of the Ph chromosome, the first chromosomal anomaly to be regularly associated with a human neoplastic disease. CGL is predominantly a disease of the productive middle years of life, which maximizes its adverse impact on family life and family economics. The disease is of worldwide distribution and there is a slight male preponderance. The disease is characterized by an initial chronic phase when it behaves as a differentiated neoplasm and responds very well to simple, nonintensive therapy. After a variable interval, CGL undergoes metamorphosis to a refractory phase that responds poorly or sometimes not at all to therapy, even when this is intensive. At the stage of metamorphosis a great variety of clinical and hematologic pictures occur, and CGL may mimic a myeloproliferative disease, a myelodysplasia, a subacute leukemia, AML, or ALL. The old concept of an abrupt, explosive transition from the chronic phase to a so-called blastic crisis is incorrect: this rarely occurs and in most patients who are carefully followed, CGL is observed to undergo two or more stepwise evolutions, eg, from chronic phase to an accelerated myeloproliferative phase to a phase that resembles AML. Many patients with CGL conform to an established pattern of clinical features. There is a history of insidious symptoms of anemia and of splenomegaly. The physical signs are those of pallor and marked splenomegaly, while the hematologic findings are of moderate anemia, moderate thrombocytosis, and a marked granulocytic leukocytosis with a specific differential count. The radiologic findings are typically normal. Diagnostic difficulty seldom arises with this classic presentation. The patient who is detected at an early stage of CGL may lack the history, physical signs, and fully developed hematologic picture of CGL. Before the availability of cytogenetic studies, the diagnosis could only be established with confidence by observing the patient until the typical features of the disease emerged. Also considered are the less frequent but important atypical presentations of CGL. The symptoms and complaints, findings on examination, complications and hematologic findings may depart from the typical case in a bewildering variety of ways, so that the diagnosis may be difficult, indeed, CGL is generally not the initial diagnosis that is made. When the patient with CGL has received treatment, it is usual for he or she to become asymptomatic, with no abnormal physical signs.(ABSTRACT TRUNCATED AT 400 WORDS)

Attempted suicide or hitting the nail on the head. Case report.

A case is reported of attempted suicide by hammering nails through the skull into the brain. This unique attempt at self-destruction was unsuccessful and the treatment, initially by an untrained first-aider and then by a neurosurgeon, was surprisingly simple. There were no long-term sequelae.

Case report: cutaneous manifestations of cryptococcosis.

Cutaneous cryptococcosis usually is associated with concurrent systemic infection and actually may develop before clinical manifestations of cryptococcal meningitis become apparent. It is rare for a cryptococcal infection to be localized only to the skin. A case of cutaneous cryptococcosis is described in an immunocompromised patient who initially had a rash and a positive serum cryptococcal antigen titer, but no central nervous system involvement. The papular pustular skin lesions disappeared after 8 weeks of therapy with amphotericin B, which was stopped secondary to progressive azotemia. Less than 2 months after therapy, the skin lesions recurred, again without evidence of systemic disease. Treatment with oral fluconazole resulted in a gradual resolution of the cutaneous lesions. The pathogenesis of cryptococcosis is discussed, with emphasis on the management of cutaneous cryptococcosis.

Multiple drug resistance, the MDR gene, and the law of maximum perversity as it applies to oncology: an hypothesis.

The so-called Law of Maximum Perversity, generally stated, says that when more than one outcome is possible, that which is the more adverse is the outcome most likely to occur. In medical oncology, the most obvious expression of this law is the fact that all the neoplasms that are most sensitive to cytotoxic drugs and are most curable by chemotherapy, are rare and in numerical terms are not important as causes of cancer-related deaths. Conversely, the most commonly encountered neoplasms that make up the bulk of oncologic practice and that cause over 90 per cent of cancer-related deaths, are all relatively resistant to cytotoxic agents and are virtually never curable by chemotherapy administered in standard (i.e. non-transplant) doses. It is postulated that the biological properties and the normal tissue distribution of the multidrug resistance (MDR) gene and its product p-170 glycoprotein explain the observed incidences and distribution of tumours that are sensitive or insensitive to cytotoxic agents. The normal role of MDR is to protect cells from environmental carcinogens, and the tissues that are most at risk, and most richly supplied with MDR, will produce drug-resistant neoplasms. Current attempts at MDR reversal may facilitate the treatment of some tumours that are resistant to multiple drugs but may cause severe toxic effects as a consequence of abrogating the largely unknown physiologic functions of P-170.

High levels of interleukin-6 are associated with low tumor burden and low growth fraction in multiple myeloma.

Interleukin-6 (IL-6) is a multifunctional cytokine postulated to play a central role as a growth factor for multiple myeloma (MM). We evaluated the spontaneous secretion of IL-6 in supernatants of Ficoll-Hypaque--enriched bone marrow (BM) cultures from 35 patients with MM. The levels of IL-6 were correlated with biological and clinical characteristics of the disease. High levels of IL-6 production defined a subgroup of patients with low tumor burden as determined by lower serum beta 2-microglobulin (B2M) (P = .02) and lower percentage of myeloma cells infiltrating the bone marrow (P = .003), higher synthetic rates of monoclonal protein (P = .006), and low proliferative compartments as measured by the percentage of Ki-67--positive myeloma cells. Patients with high proliferative fractions (Ki-67--positive myeloma cells > 20%) had significantly lower levels of IL-6 when compared with patients with low proliferative fractions (P = .005). Our findings do not support IL-6 as a major growth factor for MM, but demonstrate an association of high levels of IL-6 secretion with low tumor cell burden and low proliferative fraction.

Can MRI of the knee affect arthroscopic practice? A prospective study of 58 patients.

We made a prospective study of 58 patients with suspected internal derangement of the knee. They were examined by magnetic resonance imaging using 3-D gradient echo intermediate-weighted studies before having an arthroscopy. The preoperative clinical assessment was found to have a diagnostic sensitivity of 77% and a specificity of 43%, compared with 100% and 63% respectively for magnetic resonance imaging. Comparison of magnetic resonance imaging and arthroscopy confirmed the accuracy of magnetic resonance imaging in the diagnosis of internal derangement but the results for articular cartilage lesions were much less good, with a sensitivity of only 18% but a specificity of 100%. Acceptance of the magnetic resonance imaging findings could have resulted in a 29% reduction in the number of arthroscopies without missing any significant meniscal lesion.

Alveolar hydatid disease of the liver: computed tomography and transabdominal ultrasound with histopathological correlation.

The appearances of alveolar hydatid disease of the liver (AHDL) on computed tomography (CT) and ultrasound (US) were retrospectively compared with histopathological appearances in 67 patients with 100 separate lesions. The radiological features were correlated directly with the pathological specimens obtained from each patient. We conclude that the CT appearances are more specific, but that US has a role to play in mass screening in endemic areas, and intraoperatively.

Treatment of advanced refractory lymphomas with a combination of carmustine, bleomycin, teniposide, dexamethasone, and cisplatin (the BBVDD regimen). An ECOG pilot study.

Forty-four patients with relapsed, refractory malignant lymphomas (12 Hodgkin's disease, 32 non-Hodgkin's lymphoma) were treated with a combination of carmustine, bleomycin, teniposide, dexamethasone, and cisplatin (BBVDD regimen). Patients had failed at least one, and frequently two, chemotherapy regimens before admission to the study. Of the patients with Hodgkin's disease, 2 (17%) achieved complete response (CR), and 3 (25%) attained a partial response (PR) for an overall response rate (CR + PR) of 42%. Among the patients with non-Hodgkin's lymphoma there were 6 CR (19%) and 12 PR (37%), for an overall response rate of 56%. Median durations of response ranged from 2.5 months for nodular non-Hodgkin's lymphoma in PR to 28.5 + months for Hodgkin's disease in CR. In these heavily pretreated patients, the incidence of toxic effects was grade 3 (48%), grade 4 (23%), grade 5 (2%). The one death (grade 5 toxicity) was attributed to pulmonary impairment due to bleomycin. BBVDD is a moderately effective regimen for the palliation of patients with refractory lymphomas and merits further study.

Pentostatin induces durable remissions in hairy cell leukemia.

Fifty patients with hairy cell leukemia were treated with pentostatin (2'-deoxycoformycin; dCF) for a median of 3 months; 32 (64%) patients achieved complete remission (CR), and 10 (20%) patients achieved partial remission (PR), for an overall response rate of 84%. After reaching maximal response, no maintenance therapy was administered. The median duration of follow-up is now 39 months, and only four of 32 patients in CR and two of 10 patients in PR have relapsed. dCF therapy produces durable long-term, disease-free survival in patients with hairy cell leukemia.