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Nine patients with osteosarcoma were treated by chemotherapy combined with caffeine and surgery. All primary tumors showed complete histological response to preoperative chemotherapy consisting of three intraarterial infusions of cisplatin and caffeine without/with doxorubicin and two systemic high-dose methotrexate combined with vincristine. Limb-salvage surgery was performed in eight patients with marginal procedure, which led to the preservation of good limb function. Below-knee amputation was done in one patient with calcaneal osteosarcoma. There has been neither local recurrence nor lung metastasis in seven patients with conventional osteosarcoma during a median follow-up period of 28 months. Lung metastases leading to death were observed in one patient with small-cell osteosarcoma despite complete destruction of the primary tumor by preoperative chemotherapy. Chemotherapy combined with caffeine administration deserves further extensive and large-scale study in osteosarcoma.

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Two cases of lymphangiosarcoma arising in a chronic lymphedematous extremity following mastectomy (Stewart-Treves syndrome) were reported with not only standard histology, but also special study on the ultrastructure and immunohistology. These cancers developed as a result of chronic lymphedema of the involved limb following mastectomy 15 and 16 years ago, respectively, for breast carcinoma. Immunohistologic and electron microscopic examinations proved that this tumor originates in the vascular endotheliocytes, even though they are clinically chronic lesions apparently derived from the lymphatic vessels. This sarcoma develops multicentrically in an edematous arm and spreads out rapidly, so prognosis is quite discouraging in those patients. They need to be radically surgically treated without hesitation; hence, amputation, not limb-saving surgery, should be indicated.

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A 24-year-old female patient was was admitted because of urinary retention, four days after the development of rash with fever to be diagnosed as measles by a doctor. Neurological examinations showed hyperesthesia in lower thoracic regions and increased deep tendon reflexes in lower extremities. Cystometric findings revealed an areflexic bladder with normal sensation. Cerebrospinal fluid examination showed mononuclear pleocytosis and slightly elevated levels of protein. There was no significant increase in serum measles antibody titer. She regained normal voiding by conservative treatment with an indwelling catheter for four days. The bladder motor paralysis was probably due to non-transverse myelitis in sacral spinal region. Neurological complications of measles are briefly discussed.

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On twenty-three specimens from patients with osteosarcoma (biopsied tissue, resected specimens from primary and metastatic lesions), the human tumor clonogenic assay (HTCA: standard assay) as well as cultivated HTCA involving short-term cultivation of a single-cell suspension, was carried out. The percentage colony-forming ability, which was very small for standard HTCA, increased significantly when cultivated HTCA was performed. With cultivated HTCA, sensitivity tests were possible in 87% of the specimens, in contrast to only 28.6% with standard HTCA. Retrospective evaluation of the results obtained by cultivated HTCA with the clinical efficacy of anticancer drugs showed a true positive rate, 66.7%, and a true negative rate, 88.9%. This analysis revealed that drugs shown to be ineffective and that tumor cells are refractory to those drugs, so that clinical use of such drugs should be avoided.

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Human tumor colony-forming assay for the efficacy of antitumor agents, established by Salmon and Hamburger, has become the subject of vigorous investigations because of its close correlation to the clinical course in cancer patients. However there are yet no reports of this assay being applied to sarcoma of bone which is difficult to cultivate. To find out if this assay is useful or not for malignant bone tumors, especially osteosarcoma, 10 specimens obtained through biopsy, resection or thoracotomy were employed in the colony-forming assay. While 7 samples showed colony forming ability, the sensitivity tests were possible only in 3 specimens because of low rates of colony formation. The results of the 3 sensitivity tests corresponded appreciably to clinical courses of the patients; hence this assay seemed useful in planning a chemotherapeutic schedule for the treatment of osteosarcoma.

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To improve the plating efficiency (PE) of cells used in the standard human tumor clonogenic assay (standard HTCA), an HTCA was developed using single-cell suspensions obtained from short-term cultures of surgical specimens of malignant bone and soft tissue tumors of the extremities. Consequently, the percentage possibility of application for the chemosensitivity test for anticancer drugs as well as the PE improved from 29.7% to 65.7% for bone tumors (37 specimens) and from 30.0% to 72.4% for soft tissue tumors (31 specimens). In bone tumors the correlation between these drug sensitivity tests and the clinical effectiveness of the drugs was retrospectively evaluated in 17 specimens from 13 cases mainly of osteosarcoma; they were well correlated with the true positive rate (71.0%) and the true negative rate (90%). In soft tissue sarcomas, retrospective evaluations were possible only in 9 cases and their true positive and negative rated were 75.0% and 100% respectively. These results indicate that cultivated HTCA seemed to be a clinically useful chemosensitivity test: the anticancer drugs judged useless by this test were likely to be clinically useless. Drugs such as resistance-acquired or non-sensitive drugs should be excluded from multidrug combination chemotherapy in the treatment of bone and soft tissue sarcoma.

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Twenty-three specimens (biopsied tissue, resected specimens, and resected pulmonary metastases were obtained during biopsy, radical surgery, or thoracotomy from patients with osteosarcoma. Using these specimens, human tumor clonogenic assay (standard HTCA) and cultivated HTCA (HTCA using single-cell suspensions obtained from short-term cultures) were carried out. The percentage of colony-forming ability, which was very small for standard HTCA, increased significantly when cultivated HTCA was performed. With cultivated HTCA; sensitivity tests were possible in 87% of the specimens in contrast to only 28.6% using standard HTCA. We retrospectively analyzed the relationship between the results of HTCA and the clinical efficacy of agents such as methotrexate, adriamycin, cis-platinum, and vincristine, which are frequently prescribed for the treatment of osteosarcoma. This analysis revealed that if drugs are show to be ineffective by this test, they can be regarded as clinically ineffective against that specific tumor target, i.e., the tumor cells are refractory to those drugs. Thus, clinical use of such drugs should be avoided.

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