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Biomedical subjects

K Isu

Publications and source records attributed to K Isu.

33 records · Page 2Linked to original sources

[Chemotherapy using cisplatin in bone and soft tissue sarcoma].

Cisplatin was used in 14 bone and soft tissue sarcomas. Severe vomiting developed in all cases, but the duration was relatively short. Renal function was disturbed in cases with a higher total dose. This side effect was considered to be the dose-limiting factor of cisplatin. Seven cases showed high-frequency deafness but they did not complain of disturbance during conversation. In seven metastatic osteosarcomas, one was evaluated as a partial response and one as a minor response. No response was observed among three soft tissue sarcomas. Three cases of osteosarcoma receiving cisplatin in adjuvant chemotherapy have been disease-free for 4 and 46 months after resection of pulmonary metastases and for 50 months after resection of the primary tumor. We consider cisplatin to be the first-choice drug in cases resistant to adriamycin or methotrexate, but there are some problems when cisplatin is used in adjuvant chemotherapy, because of its side effects.

Adolescent↗

[Significance of surgical adjuvant chemotherapy in osteosarcoma].

The primary site of the metastasis of osteosarcoma is the lung. More than 90% of patients have died of pulmonary metastasis in one to two years. Control of osteosarcoma depend upon the prevention of its pulmonary metastasis. The introduction of chemotherapy consisting mainly of Adriamycin, high-dose methotrexate with Leucovorin rescue and Cisplatinum, dramatically improved the prognosis of osteosarcoma. In the past, when systemic chemotherapy was not available, the five-year survival rate was around 19%. In patients who receive chemotherapy with the current combination of chemotherapeutic agents (ADM, HD-MTX, VCR, CPM, CDDP), the incidence of pulmonary metastasis was low, and the five-year survival rate increased to 65%. In patients who receive chemotherapy, pulmonary metastasis may be either delayed, with a single metastasis appearing after termination of treatment (late isolated type), or early and multiple, emerging in reaction to treatment (early multiple type). It is generally accepted that post-operative chemotherapy can inhibit pulmonary micro metastasis and prove to be of great significance in improving the survival rate of patients with osteosarcoma of extremities and achieve limb salvage operation. On the other hand, effective control of the side effects of drug administration such as nausea, vomiting, alopecia, cardio (ADM) and renal (CDDP) toxicity and bone marrow suppression, is a problem that must be solved as soon as possible.

Adolescent↗

[A case report of malignant schwannoma originating from the bone].

While malignant schwannoma is encountered frequently as soft tissue sarcomas, it rarely is found to originate in the bone. We have had a case of malignant schwannoma originating from the tibia of a 47-year-old man. He died from uremia, that resulted from lung, spinal vertebral body, and lymph nodes metastases, despite surgical treatment and chemotherapy. In cases of rare bone tumors, the clinical diagnosis of tumoral manifestations originating in the bone is more important than the histopathological diagnosis.

Bone Neoplasms↗

Clear cell chondrosarcoma. A report of two cases and review of literature.

Two cases of clear cell chondrosarcoma located in the distal femur and proximal humerus are reported. Both patients were men aged 35 and 51 years. Their initial symptom was a pathologic fracture. Roentgenographically, one patient showed a purely lytic lesion and another lytic with centrally radiodensity. Microscopic examination revealed that the tumor cells have a centrally placed vesicular nucleus surrounded by a clear cytoplasm, with distinct boundaries. Their cytoplasm stained with S-100 protein by the peroxidase-antiperoxidase method. We found 36 reported cases (including the two reported here), and delineated the clinico-pathologic characteristics of the disease.

Adult↗

[Massive osteoplastic bone metastasis of hepatocellular carcinoma--a case report].

Massive osteoplastic bone tumor in hepatocellular carcinoma is very rare. A 48-year-old man was misdiagnosed as osteosarcoma of the right proximal tibia with dense sclerosis and marked periosteal spiculation. Histologically, there were many osteoids and immature trabeculi. Tumor cells with spindle nuclei were not atypical and had few mitoses. Three years later, he suddenly died of rupture of cerebral aneurysm. Autopsy revealed small hepatocellular carcinoma with distant metastases of the tibia, lumbar spine and lung. In this case, it was extremely difficult to decide whether or not we were dealing with primary malignant tumor.

Bone Neoplasms↗

Transplantation of human osteosarcoma into nude mouse--correlation between experiment results and prognosis of patients.

We have made experiments on transplantation of human osteosarcoma into nude mice, and investigated the correlation between experiment results and prognosis of donor patients. Tumor take was observed in 36 of 60 cases (60%) in the initial transplantation, 23 cases (38.3%) in the second passage and 16 cases in the serial transfer of three passages or more. Clinical prognosis was classified into three categories and analyzed. As to the correlation between positive or negative tumor take in the 2nd passage and presence or absence of metastasis, there was a significant relationship was found between tumor take and metastasis. Then, in mice with serially transplantable tumor, the correlation between experiment results and postmetastatic prognosis was investigated. In cases with low tumor growth index, persistence of zone formation and low alkaline phosphatase level, postmetastatic prognosis was good with statistical significance. Consequently, these experiments are highly useful for prediction of clinical prognosis.

Adolescent↗

[Intra-arterial chemotherapy of soft tissue sarcoma in children].

As to the treatment of soft tissue tumor in children, we have performed intraarterial infusion chemotherapy in 3 children, two of whom had rhabdomyosarcoma and one of whom had infantile fibrosarcoma, at Sapporo National Hospital. The former two patients had large and unresectable solid tumor. In the latter case, an uncommon disease of childhood, local excision was considered while sacrificing a significant degree of function in the affected part. We describe here these three cases and the effectiveness of this therapy. Intraarterial chemotherapy reduced the tumor remarkably and facilitated second-look surgery. Although transient hematuria, slight articular contracture and vasculitis were observed in each case as side effects during the therapy, they were only minimal and tolerable. Unfortunately, one patient relapsed 6 months after surgery, but two patients are still in good health without recurrence. According to the results of our study, we believe that this method can be effective for controlling unresectable primary malignant soft tissue tumor.

Antineoplastic Agents↗

[Four case reports of sarcoma combined with carcinoma].

We report 4 cases of double cancer, combined sarcoma and carcinoma. Case 1 was a 50-year-old woman, had a malignant fibrous histiocytoma in the leg and an advanced gastric carcinoma. The soft tissue sarcoma was resected and the gastric carcinoma was treated with chemotherapy. She died from pulmonary metastasis from the sarcoma. Case 2 was a 72-year-old woman with a liposarcoma in the leg and a thyroid carcinoma. Both tumors were resected, however, she died from pulmonary metastasis from the carcinoma. Case 3 was a 65-year-old man with a liposarcoma in the buttock and lung carcinoma. Both tumors were resected and he is alive and disease-free. Case 4 was a 47-year-old man with spindle cell sarcoma of the tibia and a rectal carcinoma. Both tumors were treated surgically, but he died from pulmonary metastasis from the sarcoma. We suggest that the combination of sarcoma and carcinoma is very rare and that the prognosis in these cases is very poor.

Adenocarcinoma↗

[Chemotherapy of advanced bone and soft tissue sarcoma].

The primary site of metastasis of bone and soft tissue sarcoma is the lung. Control of these sarcomas depends upon the prevention and treatment of their pulmonary metastasis. The introduction of a chemotherapy consisting mainly of Adriamycin and high-dose methotrexate dramatically improved the prognosis of osteosarcoma. However the effectiveness of chemotherapy has not yet been duplicated in soft tissue sarcomas except some childhood sarcomas. We analyzed the clinical data for pulmonary metastasis of osteosarcomas and soft tissue sarcomas. Based on these analyses, we tried to clarify the nature of pulmonary metastasis of these sarcomas and to evaluate its response to treatment, that this would yield clues to future treatment of these sarcomas.

Antineoplastic Combined Chemotherapy Protocols↗

[A histological study on osteosarcoma. Part I: Relationship between modes of osteoid formation and differentiation of tumor cells].

This study was undertaken to clarify whether the osteoid forming activity seen in osteosarcoma can be used as an index to show the degree of differentiation of the tumor. Twenty six human osteosarcomas which had been amputated in our clinics were used in this study. The whole slice of the primary tumor was stained by HE and Masson stain. The following observations were microscopically made in the peripheral, transitional and central part of the tumor; 1) the content and maturity of osteoid, 2) the degree of polymorphism and mitotic activity of the tumor cells. In 13 out of 26 cases, the amount and maturity of osteoid gradually increased toward the center of the tumor. On the other hand, the degree of polymorphism and mitotic activity of tumor cells in these cases gradually decreased toward the center. Mitotic activity in the center of the tumor decreased to about half of the peripheral part. The clinical courses of these 13 cases were milder than those in which the gradual increase of the amount and maturity of osteoid toward the center of the tumor were not observed. These results showed that zone formation of osteoid maturity in osteosarcoma can be used as an index to show the degree of differentiation of the tumor.

Adolescent↗

Characteristics of human soft tissue sarcomas in xenografts and in vitro.

Two permanent, transplantable strains of rhabdomyosarcoma (SAS) and synovial sarcoma (KUSHI) were established by transplanting them serially into nude mice. The original SAS tumor and its transplant were histologically identical and gave an appearance of so-called embryonal rhabdomyosarcoma. The KUSHI tumor changed after the second passage, showing the biphasic pattern of synovial sarcoma, while undifferentiated myoblast-like cells were observed throughout the original tumor. Three in vitro cell lines from the SAS and one from the KUSHI tumor were successfully established. The human origin of the SAS and KUSHI transplanted tumors could be verified by the presence of human chromosomes. The cells cultured from the SAS tumor were more sensitive to anticancer drugs than those of the KUSHI tumor. However, as the number of serial passages on nude mice increased, the sensitivities of the SAS cells decreased, while those of the KUSHI cells increased. The modal chromosome number of the SAS tumor changed from 51 to 49 to 46 during serial passages on nude mice. These observations suggest that the sensitivities to anticancer drugs not only differ among soft tissue sarcomas of different histologic types, but also change continuously during the growth of the tumor itself.

Animals↗

Analysis of osteoid-forming activity of human osteosarcoma implanted into nude mice.

Thirty cases of human osteosarcoma were transplanted subcutaneously in BALB/c nude mice. Twenty-four tumours survived in animals and showed the histopathology of the original tumours. Growth of transplantable tumours was closely related to the amount of osteoid tissue and tumours with predominant osteoid tissue showed slow growth. Tumours whose osteoid-forming activity tended to diminish or disappear were likely to fail early during serial transplantation. Two osteosarcoma (SU and ISHI) were established into permanent transplantable strains and were maintained in nude mice for more than three years. These two strains showed striking differences in their growth capacity; SU grew rapidly and frequently formed pulmonary tumours after tail vein injection of tumour cells. Histologically, ISHI osteosarcoma cells continue to form osteoid tissue, whereas SU cells showed anaplastic changes and lost osteoid-forming activity. Alkaline phosphatase and Lactate Dehydrogenase (LDH) activities of tumour tissue were lower in ISHI than SU, and significant elevation of the relative value of Fraction III of LDH isozyme has been demonstrated in SU, and Fraction IV in ISHI. On this basis, the authors discuss the relation between the amount of osteoid formation or LDH isozyme patterns and the malignant potential of human osteosarcoma.

Alkaline Phosphatase↗

[A study on the treatment of pulmonary metastatic osteosarcoma].

The primary site of metastasis of osteosarcoma is the lung. Even if a primary lesion was completely removed by radical surgery, more than 90% of the patients died of pulmonary metastasis in one to two years in the past. A control of osteosarcoma depends upon the prevention and treatment of its pulmonary metastasis. An introduction of chemotherapy consisting mainly of adriamycin and high-dose methotrexate dramatically improved the prognosis of osteosarcoma. We analyzed the clinical data, and gross as well as histopathologic post mortem findings, in 161 cases without chemotherapy and 42 cases with systemic adjuvant chemotherapy. Based on these analysis, we tried to clarify the nature of pulmonary metastasis of osteosarcoma and to evaluate its response to treatment from a standpoint of clinical pathology, hoping that this would yield a clue to future treatment of osteosarcoma.

Antineoplastic Agents↗

A preliminary report of neoadjuvant chemotherapy NSH-7 study in osteosarcoma: preoperative salvage chemotherapy based on clinical tumor response and the use of granulocyte colony-stimulating factor.

Eleven patients with high-grade osteosarcoma of an extremity were treated with neoadjuvant chemotherapy with NSH-7 protocol. NSH-7 is a refinement of the T-12 Rosen protocol. Preoperative chemotherapy is initiated with a doxorubicin (ADM) and high-dose methotrexate combination. If the primary tumor progresses after the first cycle, the preoperative chemotherapy is switched to a combination of cisplatin and ADM. Postoperative adjuvant chemotherapy was selected based on histological response of the primary tumor. In addition, recombinant human granulocyte colony-stimulating factor was used to prevent leukocytopenia and to increase the dose intensity of the chemotherapy. In 1 patient, preoperative chemotherapy was switched to salvage treatment. Of the 156 courses given, there were 10 delays and 4 dose reductions. Leukocytopenia accounted for only 1 delay. All 11 patients completed the chemotherapy and 5 patients were fully able to tolerate the protocol without delay or dose reduction. Nine patients remained alive and continuously free of disease at an average follow-up of 35 months. The rate of continuous disease-free survival at 3 years was 81%, which was significantly better than that of the T-12 study of our group. These observations suggest that the NSH-7 protocol is a safe and effective treatment regimen for osteosarcoma.

Adolescent↗

An in vitro method for testing the sensitivities to drugs of human osteosarcomas grafted onto nude mice.

Sensitivities to anticancer drugs were tested with cultured cells from six osteosarcomas transplanted onto nude mice and those of six human osteosarcomas cultured in vitro directly from the original tumor. The suppression by the anticancer drugs of 3H-TdR incorporation into the cultured cells was examined. The cells that had been grafted onto nude mice were highly sensitive to ADM and MMC and less sensitive to BLM and MTX in all of the tumors tested. Similar results were obtained with cells cultured directly in vitro from the original tumor. These results were somewhat comparable with those achieved by measuring cell survival and the success of back transplants onto nude mice after treatment with drugs. If further information on appropriate labeled precursors can be developed, testing the sensitivity of tumors to drugs by measuring the suppression of nucleic acid synthesis should prove useful in clinical applications.

Animals↗