Tetany: a complication of cis-dichlorodiammineplatinum(II) therapy.
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Biomedical subjects
Publications and source records attributed to C B Pratt.
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The kinetics of methotrexate were followed in a patient given two 6-hr infusions of 400 mg/kg in the presence and absence of a pleural effusion. Although the decline in serum concentrations during the first 30 hr after the infusion was similar for the two treatment courses, the half-life beginning 30 hr after the infusion was 6.7 hr without the pleural effusion and 14.4 hr with the pleural effusion. Comparison of the intercompartment distribution rate constants indicated slower movement of the drug back into the central compartment from the peripheral compartment when a pleural effusion was present. Pleural fluid methotrexate concentrations were consistently higher than serum concentrations. These data indicate that the increased risk of toxicity following high-dose methotrexate in patients with pleural effusions is due to changes in methotrexate kinetics resulting in delayed excretion.
Nodular renal blastema and nephroblastomatosis were present in 8 of 118 patients (6.8%) with Wilms' tumor. Five of these 8 patients (63%) had bilateral Wilms' tumors. Two had hemihypertrophy. Preoperative renal angiograms were accurate in detecting these metanephric anomalies. The surgical approach consisted of removal of the most diseased kidney and biopsy for diffuse tumors and wedge resections for localized tumors for the remaining kidney. Postoperatively, radiation was administered when tumor extended outside the kidney. Chemotherapy consisted of vincristine and dactinomycin for 18 mo and adriamycin for 6 mo. This method of management resulted in tumor-free survival of these 8 patients for 1--44 mo (median 24 mo). Nodular renal blastema and nephroblastomatosis may possibly develop into Wilms' tumor. All of these three conditions respond to surgery, chemotherapy, and radiation. When a Wilms' tumor is encountered, it is better to explore and possibly biopsy the opposite kidney. There is a place for second-look laparotomy in this spectrum of congenital anomalies.
The ultrastructural features of a malignant histiocytoma of the acromial process of the scapula were studied. Material was obtained from two surgical biopsy specimens and an amputation specimen from the tumor. Cells possessing characteristics of histiocytes, fibroblasts, xanthoma cells, and multinucleated giant cells were present throughout the tumor. Smaller numbers of undifferentiated cells and lymphocytes were also observed. Intimate cytoplasmic interdigitations between adjacent tumor cells were found, and instances of degenerating intracytoplasmic cells, possibly representing phagocytosis, were observed. Specimens stained with periodic acid-Schiff reagent with and without exposure to diastase, examined by light microscopy, showed that numerous cells contained phagocytized material consisting of degenerating cells rather than cytoplasmic glycogen. Intraumor lymphocytes apparently represented an inflammatory reaction to the tumor. The tumor giant cells and xanthoma cells were probably modified histiocytes. Results of the study were compared with previous reports of ultrastructural studies of malignant histiocytoma of soft tissues. Fundamental similarities between such studies and this one suggested that the progenitor cell is a histiocyte, whether arising in bone or in soft tissues, and that the progenitor cell is capable of differentiation in both histiocytic and fibroblastic directions.
Twenty-three children with advanced cancer refractory to conventional therapy received weekly iv doses of neocarzinostatin for 5 weeks. Doses were escalated from 500 to 6750 units/m2/week. Four types of toxic manifestations occurred: acute reactions consisting of shaking chills with or without fever and cyanosis (rigor), hypersensitivity, vomiting, and marrow depression. Evidence of oncolytic activity was limited to patients with acute leukemia in whom phase II trials at doses between 3000 and 4500 units/m2 appear warranted.
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Rhabdomyosarcoma of the head and neck often presents with vague symptoms which mimic other disease conditions. These factors lead to undue delay in the establishment of the correct diagnosis and the delivery of acceptable therapy, including surgery, radiation therapy, and chemotherapy. There is, however, evidence of improved results of treatment of these tumors since the addition of multiple drug chemotherapy to surgery and radiotherapy.
Because of the great risk for development of pulmonary metastases following amputation for osteosarcoma, 24 consecutive patients with "clinically localized" osteosarcoma of an extremity were given adjuvant combination chemotherapy with adriamycin-cyclophosphamide-high-dose methotrexate-citrovorum factor. Thirteen of these patients remain free of tumor from 11 to 48 months following amputation. The median disease-free survival is estimated to be 18 months and the median survival 27 months. No relapses have been observed in any patients surviving free of disease beyond 23 months. Combination chemotherapy was also given to 16 patients whose disease was not localized; eight with pulmonary metastases at or following diagnosis, one with nodal metastases at diagnosis, two with osteosarcoma following radiation therapy for other malignant tumors, three with osteosarcoma of flat bones, one with parosteal osteosarcoma, and one with multifocal osteosarcoma. Three of this latter group of patients are surviving free of tumor at 8, 17, and 19 months from diagnosis. Two young patients died from complications of methotrexate and adriamycin toxicity.
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Between October, 1974 and December, 1976, 13 adolescent patients with far-advanced, poorly differentiated colorectal carcinoma had been referred to a pediatric cancer center. All patients received chemotherapy with vincristine, methyl-CCNU and 5-fluorouracil. Five of 13 patients are living, one of whom remains disease-free after 12 months of chemotherapy. Four of the patients were from urban areas and nine from rural areas. One of four from urban areas had intimate exposure to chemicals used in the production of cotton and soy beans. Eight of nine patients from rural areas also had exposure to farm or agricultural chemicals, and three of these patients were intimately involved with the spraying operations. Suggestions regarding etiology and causative factors for the development of carcinoma of the colon in adults have previously been advanced. Results of these studies suggest that alternate etiologies must be suggested for adolescent colorectal carcinoma.
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The eradication of microfoci of metastatic osteosarcoma by adjuvant chemotherapy permits the surgeon to take a more conservative approach to amputation and to more aggressively resect metastases. In a series of 59 children with osteosarcoma of an extremity, transmedullary amputation carried no greater risk of stump recurrence than either disarticulation or amputation above the joint. We attribute this to careful selection of the level of amputation by use of preoperative bone scans, intraoperative frozen sections of bone stump and intensive postoperative adjuvant chemotherapy. Immediate application of a prosthetic limb has enhanced the physical and emotional rehabilitation of these patients. Resections of pulmonary metastases in 12 patients who were receiving adjuvant chemotherapy has resulted in a median tumor-free survival of 17 mo, with 3 patients still alive without disease for 13, 25, and 72 mo. A more aggressive approach to the resection of pulmonary metastases may substantially improve current rates of tumor-free survival.
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Treatment for the child with cancer has increasingly been on a rational rather than an empiric basis. An understanding has developed of the importance for determining clinical and laboratory features present at diagnosis as an aid not only to establish a prognosis but also to design specific treatment regimens. A system has been developed for bringing new chemotherapeutic agents into clinical trials as effectively as possible. Through both clinical and laboratory studies, an increasing understanding of the biology of cancer is being developed. This understanding will provide the basis for more rational treatment programs in the future. Physicians of different specialty interests have learned to work together to develop coordinated programs of treatment so important to optimal care. By far the most important lesson learned, however, is that cancer in children is not of necessity a fatal disease, even when dissemination has occurred. For the furture, it will be necessary to develop even more effective methods of treatment, and research must provide a better understanding of this disease that may offer the opportunity for prevention, which, after all, is the number one interest of the pediatrician.
A 5-year survivor of disseminated metastatic rhabdomyosarcoma arising from the paratesticular tissues is reported. Each of the 6 patients with paratesticular rhabdomyosarcoma treated at this hospital has been free of disease from more than 2 months to more than 7 years. The unusually good prognosis associated with this site may be owing to early detection, predictable pathways of initial lymphatic dissemination and aggressive surgical treatment followed by radiotherapy and multiple agent chemotherapy.
An 11-year-old Caucasian girl who had been cured of bilateral retinoblastoma developed non-radiation-induced osteosarcoma in multiple sites of the extremities. Investigation of the medical histories of 36 of her family members through six generations revealed that 8 relatives on the maternal side (22%) had malignant tumors, predominately genitourinary carcinomas, 2(6%) had benign tumors only, and 2(6%) had both benign and malignant neoplasms. The histologic variety of these tumors, the predominance of genitourinary carcinoma, the higher than expected frequency of tumor appearance over six generations, and the occurrence of malignant tumors in direct lineage suggest that the case of retinoblastoma followed by osteosarcoma is part of a familial cancer syndrome.
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Four white women who developed osteosarcoma during pregnancy were referred for treatment, 2 prior to delivery and development of metastases, and 2 after delivery and development of metastases. After amputation, these patients received combination chemotherapy with either vincristine-cyclophosphamide or adriamycin-cyclophosphamide followed by high-dose methotrexate with leucovorin rescue. Two patients survived, 1 tumor-free and 1 with bony and soft tissue metastases. Management of pregnant patients with osteosarcoma should include the use of adjuvant systemic chemotherapy to prevent detectable metastases. This treatment should follow amputation or resection and early termination of pregnancy.