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An aorta-derived inhibitor of endothelial cell and tumor cell growth and medroxyprogesterone, which depresses collagenase expression in vivo, were tested alone and in combination against B16-F10 melanoma in C57BL/6 mice in such doses that either agent alone had little effect. Together, these agents retarded growth of subcutaneously transplanted tumor cells and reduced the number and size of pulmonary tumors after iv tumor cell injection. Of the treatments used, only the aortic factor administered alone prolonged life in mice with pulmonary tumors.

A total of 108 patients with mammary duct ectasia have been reviewed. Patients who presented with breast pain or a lump were significantly younger than those with nipple retraction. A histological review of the 88 patients who underwent biopsy showed severe periductal inflammation around non-dilated ducts occurred in younger patients and was associated with the symptom of breast pain or a lump, whereas older patients had duct dilatation as the most prominent feature, frequently associated with nipple retraction. These findings suggest periductal mastitis precedes duct dilatation and is the initial disorder in this condition. Data on parity and breast feeding for the 108 patients with duct ectasia were compared with age-matched groups of 505 patients with breast cancer, 199 with fibroadenoma, 240 with cysts and 912 ‘normals’. There were no differences in parity or breast-feeding history between the patients with duct ectasia and any other group, indicating that neither parity nor breast feeding is an important aetiological factor in this condition.

Thirteen patients with metastatic colorectal adenocarcinoma underwent treatment with continuous ambulatory 5-fluorouracil (5-FU) infusion 300 mg/m2/day and intermittent bolus methotrexate (MTX) (200 mg/m2) with calcium leucovorin (LCV) 10 mg/m2 orally every 6 h X four to eight doses given 24 h after MTX. Although MTX administration was planned every 14 days, the average time between treatments exceeded 19 days (range 14-42) because of excessive toxicity. All patients experienced toxicity at some time in their treatment course, requiring interruption of 5-FU infusion in 12 of 13 patients. Significant toxicities included stomatitis (13 of 13 patients), hand-foot syndrome (8 of 13 patients), and diarrhea (3 of 13 patients). Toxicity did not appear to be minimized by attenuation of MTX and/or 5-FU dosage or by increasing the dose and/or duration of LCV. At this dosage schedule the addition of MTX/LCV to 5-FU infusion results in excessive and unacceptable toxicity and does not appear to improve treatment results.

As part of a programme of assessment of the ‘Sterotix' localisation device, aspiration cytology was carried out on 50 patients with 52 impalpable, mammographically detected breast lesions using the stereotaxic guidance device. This was followed by an open localisation biopsy of the area for confirmation. In 12 patients (23%) the aspirations failed to yield sufficient material for diagnosis. This was frequently due to the poorly cellular nature or very small size of the lesions. Of the remaining 40 patients, 15 were regarded as having both mammographically and cytologically benign changes which were confirmed histologically; they could thus have been spared diagnostic surgery. Ten patients had a diagnosis of malignancy with both investigations, and could have had planned investigation and subsequent definitive surgery. Of the remainder, 14 lesions had a report of malignancy or suspicion of it with either technique and these patients would have come to conventional localisation biopsy. Only one patient was found to have a malignancy, who had cytologically benign and mammographically ‘probably benign' disease: this was an invasive lobular carcinoma with a dominant in-situ component and may well have been an incidental finding on biopsy.

Between 6/81 and 6/83, 73 patients with small cell carcinoma of the lung were treated according to a prospective protocol in which cyclophosphamide, doxorubicin, and vincristine (CAV) were given concurrently with prophylactic craniocervical irradiation to the level of C5. Both limited and extensive disease patients with normal computed tomography of the brain received 25 Gy in 10 fractions in 2 weeks. Complete responders to CAV received consolidative thoracic irradiation (CTI) to the local-regional primary (37.5 Gy in 15 fractions in 3 weeks), the first 25 Gy in 10 fractions serving as prophylaxis of the C6 to T12 spinal cord. The neuraxis from L1 to S2 then received 25 Gy in 10 fractions in 2 weeks. Consolidative irradiation of localizable metastatic sites was given in extensive disease patients. Partial and nonresponders to CAV received 50-60 Gy in 5-6 weeks to local-regional disease. With a median followup of 29 months, survival was significantly better (p less than .01) in patients receiving CTI to the chest after complete response to CAV (both limited disease and extensive disease) than without CTI. Of 41 patients completing the protocol and without central nervous system (CNS) involvement at presentation, four (9%) failed initially in the CNS (two brain, two spinal axis); CNS failure was the cause of death in all four patients with no other sites of metastases at death in two of these. Failure to complete protocol treatment was due to disease progression during chemotherapy in 25/73 (34%) and chemotherapy related complications (three sepsis, one gastrointestinal bleed) in four of 73 (5.5%) patients. CTI and prophylactic neuraxis irradiation did not increase morbidity or result in mortality in the sequence utilized; prophylactic neuraxis irradiation appears to reduce the CNS relapse rate, and CTI benefits survival.

We studied renal function and serum electrolytes in 51 patients receiving cisplatin chemotherapy by retrospectively reviewing the charts of 44 patients and prospectively following seven patients. Hypomagnesemia developed in 23 of 44 evaluable patients who were receiving cisplatin. We documented inappropriate renal magnesium wasting in four patients. Two patients required hospitalization for symptomatic hypomagnesemia. We conclude that cisplatin can induce a renal tubular defect in magnesium conservation and serious clinical syndromes of magnesium deficiency.

In this study breast tissue that contained ultrastructural dense core granules has been examined from 24 patients. The possible neuroendocrine characteristics of the granules were studied using the uranaffin reaction and an ultrastructural argyrophil stain. The tissue included 15 breast carcinomas and nine benign samples. Two types of breast dense core granules can be distinguished on the basis of intracellular distribution patterns and histochemical reactivity. Type I dense core granules are the most common and they were found subluminally distributed in non-pathological tissues and benign lesions as well as carcinomas. They were uranaffin-negative and are unlikely to be of endocrine nature. Type II dense core granules were found only in four carcinomas, where they occurred abundantly throughout the cytoplasm. These granules were uranaffin-positive and argyrophilic and thus exhibited characteristics consistent with neuroendocrine structure.

This report details the outcome after clinical diagnosis of mammary fibroadenoma in 110 women aged under 35 years. After fine needle aspiration cytology, and subsequent exclusions and failures of follow-up, 92 lesions were observed for a mean of 47 weeks (range 13–90 weeks), with regular measurements until removal of persisting lesions at 12 months. Fifteen lesions disappeared and 56 had the classical histology of fibroadenoma, mean size 2·5 cm; 30 of the latter continued to grow throughout the study. Cytology is essential to exclude malignancy if conservative treatment is considered, and is helpful in identifying a benign lesion. A period longer than 12 months may be required for resolution of a fibroadenoma and removal under local anaesthesia as a day case offers a simple alternative.

Excerpt To the editor: A typographic error was made in the article entitled "Testicular Germ-Cell Neoplasms: Recent Advances in Diagnosis and Therapy" (1) in the March 1979 issue. The first sentenc...

A classical osteogenic sarcoma of the breast is described and the results of light microscopy, including immunohistochemistry for epithelial and mesenchymal markers, and of electron microscopy are presented. No epithelial features were detected by any of the methods used, the tumour being considered a true osteogenic sarcoma. The tumour appears to have arisen de novo, and not from a pre-existing fibroadenoma.

The mammograms and specimen radiographs of 45 women in whom the presence of microcalcification played a major part in the decision to biopsy, were studied to determine possible distinguishing features. A mammographic lesion of 150 mm 2 or less with an irregular density and five or more calcific particles, especially if palpable, was very likely to be an invasive carcinoma. With improved resolution, it should become possible to distinguish those calcifications covering 150 mm 2 or less in the mammograms which are associated with parenchymal structures and those that are associated with stromal elements. Features that may potentially distinguish some benign parenchymal calcifications and those parenchymal calcifications associated with non-invasive malignancy are described. There will probably remain a few benign parenchymal associated calcifications which are identical to the calcifications associated with non-invasive cancer. Implications for improvement in technique are considered.

The diagnosis and treatment of testicular neoplasms have been facilitated by identification of the tumor-associated proteins alpha-fetoprotein and human chorionic gonadotropin. These circulating tumor markers, present in 85% to 90% of patients with nonseminomatous testicular cancer, reflect tumor presence and reliably indicate response to therapy. Alpha-fetoprotein is produced by embryonal carcinoma and yolk-sac tumors; human chorionic gonadotropin is produced by syncytiotrophoblastic giant cells and the syncytiotrophoblastic component of choriocarcinoma. Refinements in staging techniques and definitions have improved prognostication. Effective therapy for seminoma (cure rate, greater than 90%), early-stage (stage I, stage IIN1-2) testicular carcinoma (cure rate, 65% to 87%), and advanced (stage IIN3-4, stage III) testicular carcinoma (complete remission rate, 50% to 74%) has been shown in clinical trials. Adjuvant chemotherapy/radiotherapy trials for limited stages of testicular carcinoma, and further experience with intensive chemotherapy-based trials for advanced stages may further improve the prognosis for all testicular germ-cell neoplasms.

Fourteen patients with advanced gastric adenocarcinoma were treated with continuous 5-fluorouracil (5-FU) infusion, 300 mg/m2/day, through an indwelling central venous catheter; 13 were evaluable for response. The results were as follows; Partial remission was seen in 4 of 13 patients (31%), stable disease in 5 of 13 patients (38%), and progressive disease in 4 of 13 patients (31%). The median duration of response was 19 weeks (range, 10-41), and the median survival for all patients from initiation of infusion was 27 weeks (range, 9-54). Treatment interruption and/or dosage attenuation for toxicity was necessary in 7 of 14 patients (50%); however, myelosuppression, alopecia, and nausea and vomiting were not observed. 5-FU infusion is well-tolerated, palliative therapy for patients with advanced gastric carcinoma and may warrant further investigation in combination with other chemotherapeutic drugs.

“ ‘Running a big business’, the Clerk to the Governors of St. Thomas's Hospital was once quoted as saying, ‘is a piece of cake compared with running a hospital’.” Spencer, J.A. (1967). Management in Hospitals. London: Faber.

Background: We have previously demonstrated that breast cancers associated with inherited BRCA1 and BRCA2 gene mutations differ from each other in their histopathologic appearances and that each of these types differs from breast cancers in patients unselected for family history (i.e., sporadic cancers). We have now conducted a more detailed examination of cytologic and architectural features of these tumors. Methods: Specimens of tumor tissue (5-µm-thick sections) were examined independently by two pathologists, who were unaware of the case or control subject status, for the presence of cell mitosis, lymphocytic infiltration, continuous pushing margins, and solid sheets of cancer cells; cell nuclei, cell nucleoli, cell necrosis, and cell borders were also evaluated. The resulting data were combined with previously available information on tumor type and tumor grade and further evaluated by multifactorial analysis. All statistical tests are two-sided. Results: Cancers associated with BRCA1 mutations exhibited higher mitotic counts (P = .001), a greater proportion of the tumor with a continuous pushing margin (P

Burkitt lymphoma is a unique tumor because of its unusual growth characteristics and its potential for allowing patients long-term survival with the use of single-agent chemotherapy. Previous reports have identified unusual and serious metabolic abnormalities that are a consequence of the basic disease and its treatment, including hyperkalemia, 1 hyperuricemia, 2 and lactic acidosis. 3 In this report, we describe two patients with Burkitt lymphoma in whom we encountered two previously unrecognized, to our knowledge, serious metabolic complications of the treatment of this disease, hyperphosphatemia and hypocalcemia. Recognition and management of these complications during the initial phase of therapy may prove lifesaving for the patient. Patient Summaries Patient 1. —A white boy, 6 years 9 months old, was admitted to the National Cancer Institute in August 1967 for evaluation and therapy of Burkitt lymphoma. The patient had complained of intermittent nonspecific abdominal pain for several months and four weeks prior

A man with long-standing common variable hypogammaglobulinemia was treated with chemotherapy and local radiation for diffuse mixed lymphoma. He continues in complete remission 42 months after the completion of therapy. Vigorous therapy for lymphoma can be used in the face of preexistent immunodeficiency. Complete staging and appropriate combination chemotherapy or radiation therapy should be carried out for lymphomas that occur in certain immunodeficient patients. ( Arch Intern Med 1982;142:90-92)

• A three-year review of the medical records of 76 patients with apparent thalassemic syndromes (mean corpuscular volume, 5 × 10 6 /cu mm) was performed to assess overall physician response to this information at a midwestern teaching institution. Abnormal indices were recognized in only 50% of the cases; in only 32% of cases was a thalassemic syndrome considered in the differential diagnosis. Residents in internal medicine failed to recognize microcytic indices and to consider thalassemic syndromes 42% and 59% of the time, respectively. Even though hemoglobin electrophoresis was performed in 25 patients, in only 15 (56%) of the 25 cases was β-thalassemia proved or α-thalassemia presumptively diagnosed. In 17% of all cases, the patients were treated with iron without diagnostic findings on iron studies and/or in spite of data suggesting a thalassemic syndrome. The RBC indices are an underused portion of the complete blood cell count, and readily apparent thalassemic syndromes are often not considered. ( Arch Intern Med 1985;145:93-94)

Excerpt Intravenous administrations of high-dose gammaglobulin increases the peripheral blood platelet counts of most patients with idiopathic thrombocytopenic purpura (1-8). The mechanism of this ...

A prospective, randomized, controlled, double-blind study was performed between 1982 and 1985 to assess the ability of ketoconazole to prevent fungal infections in selected patients with cancer. Fifty-six patients receiving induction chemotherapy for acute leukemia, autologous bone marrow transplant for refractory nonhematopoietic malignant neoplasms, multidrug chemotherapy for malignant lymphoma, or corticosteroids for brain metastases were randomized to receive either oral ketoconazole, 400 mg/d, or placebo and observed until leukopenia resolved or corticosteroid therapy was stopped. Oral candidiasis developed in eight (28%) of 29 patients receiving placebo compared with none of 27 receiving ketoconazole. However, ketoconazole failed to prevent Candida esophagitis and vulvovaginitis in two patients and one patient, respectively. Furthermore, prophylactic use of ketoconazole did not significantly alter the total number of hospital days, febrile days, or antibiotic days or the requirement for amphotericin B in patients with acute leukemia and autologous bone marrow transplant. Since oral candidiasis can be successfully managed by several different treatment modalities when it does occur, we do not think that the routine prophylactic use of ketoconazole is justified.

Dr Bessman and Drs Karnad and Poskitt make valid points about the utility of the RDW in the evaluation of microcytic anemias. Although it is now available in our hospital, this was not utilized at the time that we initiated our study. However, it seems unlikely that clinicians who fail to recognize an abnormally low MCV will know how to utilize an abnormal RDW. This further emphasizes the most important point of our study—that the diagnostic approach and evaluation of microcytic anemias needs to be improved for physicians in general. Dr Feeley makes an important point about the greater effectiveness of a written note over computer flagging of aberrant results in laboratory data. However, in spite of the volume of information provided, it is still up to the clinician to determine the relative importance of all abnormal laboratory data and to decide which, if any, additional diagnostic tests are indicated.

• A 36-year-old woman, presenting with fever, pancytopenia, hepatosplenomegaly, and striking effacement of the bone marrow by true malignant histiocytes, was found to have no benefit from the systemic administration of cyclophosphamide, vincristine sulfate, doxorubicin, prednisone, and highdose methotrexate with calcium leucovorin rescue. Striking histologic and clinical Improvement was noted after the administration of two cycles of etoposide and amsacrine, each cycle consisting of 100 mg/sq m/day of each agent for five days. We believe that this therapy should be considered for future patients demonstrating aggressive presentations of malignant histiocytosis. (Arch Intern Med1985;145:742-743)

(1) Differences in meadow vole population densities were attributed to nutrient treatment effects on habitat quality; densities were low in communities with low plant species diversity and poor ground cover. (2) Survivorship was decreased in wheat field fertilized treatments, apparently due to poor vole habitat quality, although net primary production was significantly increased. (3) There was no evidence of toxic effects of sludge on vole population density, survival, or reproductive parameters. (4) Sex ratios favoured females in high food-quality habitats and males in low food-quality habitats.