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We report a case of postoperative recurrence of thymic carcinoma that was effectively treated with combination chemotherapy of nedaplatin(NDP)and docetaxel(DOC). We performed thymectomy for thymoma in a 55-year-old man. The pathological diagnosis was squamous cell thymic carcinoma(pT3N0M0, Stage III). The patient was observed without postoperative radiotherapy being administered. Six months after the operation, the patient was admitted to our department with carcinomatous pericarditis. Whole-body examination revealed multiple lung and liver metastases and a left femoral metastasis. After pericardiocentesis, radiation therapy was administered for the left femoral metastasis. Combination chemotherapy (NDP[60mg/m2]/DOC[70mg/m2])was administered for the multiple lung and liver metastases. After 4 cycles of chemotherapy, the multiple lung metastases were completely resolved and the liver metastases were clearly reduced. Partial response and acceptable toxicity were identified. Thymic carcinoma is a rare epithelial neoplasm for which the optimal chemotherapy regimen has not yet been established. Combination chemotherapy with NDP/DOC was effective in the case of our patient with postoperative thymic squamous cell carcinoma recurrence, and it can be considered as a promising regimen for patients from the standpoint of clinical efficacy.

The efficacy and safety of bi-weekly administration of medium-dose docetaxel (TXT) were evaluated in patients with advanced and recurrent breast cancers. The additional effect of 5'-DFUR for non-responders was also evaluated. Forty patients with advanced and recurrent breast cancers were treated and 38 cases of 40 were evaluated (34 with recurrent cases and 4 with advanced cases). All cases were female, and their mean age was 56.0 (38-74). TXT of 60 mg/body, which was equivalent to 30-50 mg/m2 for standard-sized Japanese women, was administered every two weeks. 5'-DFUR of 800 mg/body was added for non-responders after 5 weeks. The response rate was calculated from the data of 32 cases with measurable lesions, and side effects were evaluated in about 34 cases with exact records. Two hundred seventy-one courses were performed for 38 patients (4-24 courses per person, average 7.13 courses). The mean dosage per course of TXT was 58.4 mg/body (38.3 mg/ m2). Three complete and 7 partial responses were observed (overall response rate: 31.3%). Ten non-responders were evaluated for the additional effect of 5' DFUR, and one case reached PR. Grade 3/4 bone marrow suppression occurred in 9 patients, and Grade 3/4 general malaise was observed in two patient. According to the results, bi-weekly administration of medium dose TXT is an active and safe regimen in patients with advanced and recurrent breast cancers. The additional effect of 5'-DFUR was observed in one of 10 non-responders of bi-weekly chemotherapy with medium-dose TXT.

We examined replication error (RER) and loss of heterozygosity (LOH) in the region of microsatellites in 60 cases of resected lung cancer. We used microsatellite probes for the short arm of the 2nd chromosome (D2S123, D2S136), the short arm of the 3rd chromosome (D3S1067), and the short arm of the 17th chromosome (TP53). According to stage, the frequency of LOH was 25% in stage I, 33% in stage II, 44% in stage IIIA, 11% in stage III B, and 63% in stage IV. According to histological classification, the frequency of LOH was 41% for squamous cell carcinoma, 24% for adenocarcinoma, and 100% for small cell carcinoma. According to microsatellite probe results, the frequency of LOH was 6.7% for D2S123, 5.0% for D2S136, 16.7% for D3S1067, and 18.3% for TP53. Two of the 60 cases showed RER. One case was stage I squamous cell carcinoma, and the other was stage IV adenocarcinoma. Except for stage III B,LOH in the microsatellite region increases with the stage. LOH is often detected in the order of small cell carcinoma, squamous cell carcinoma, and adenocarcinoma. According to the chromosome number, LOH is detected more often in the 3rd and 17th chromosomes than in the 2nd chromosome. In 20 cases with LOH, only two showed DNA diploidy. Compared to LOH of the microsatellite region, DNA content analysis by flow cytometry has accuracy problems.

To investigate the effect of intra-arterial injection of mitoxantrone emulsified with ethiodized oil, forty-eight patients with hepatocellular carcinoma were evaluated. After the treatment, ten of the patients underwent hepatectomy. In the thirty-eight unresected cases, there were 15 (39%) partial responses, which continued 1.2 to 11.8 months (mean, 5.8 months). The 1- and 2- year survival rates were 67% and 38%, respectively. The response rate was higher in cases with tumor under 5 cm in diameter. In the remaining 10 resected cases, the necrotic areas in main nodules ranged from 65% to 100% (mean, 85%). This treatment might be applied effectively to patients with small hepatocellular carcinoma.

We quantitatively analyzed the c-myc and p53 products using flow cytometry in 28 cases of resected lung cancer and one case each of chorio-carcinoma, plasmacytoma, malignant mesothelioma and sclerosing hemangioma. In the lung cancer cases, c-myc and p53 products were detected in 10 cases (35%) and 7 cases (21%), respectively. These rates are higher than the DNA abnormal expression rates of the c-myc and p53 genes (15% and 12%, respectively) in our own data. In the adenocarcinoma of lung cancer cases, c-myc and p53 products were detected in 9 cases (53%) and 5 cases (29%), respectively. Among the squamous cell carcinoma cases, there were one case (11%) of c-myc expression and one case (11%) of p53 expression. DNA content analysis of the lung cancer patients revealed 7 cases of DNA diploidy and 21 cases of DNA aneuploidy. All 10 c-myc-positive cases showed DNA aneuploidy; thus the positive rate for c-myc products in the DNA aneuploidy cases was significantly different compared with the DNA diploidy cases (p < 0.05). In the sclerosing hemangioma case, we detected both c-myc and p53 products. Sclerosing hemangioma has been thought to be a benign tumor, but it may be a malignant tumor.

Mitoxantrone (MIT) is a new anthraquinone anti-cancer agent. We successfully treated 3 patients with locally advanced breast cancer, including two inflammatory breast cancers, by pre-operative arterial injection of MIT. The treatment protocol was MIT 12 mg/m2 injected into both the internal mammary and the subclavian artery with oral administration of 5' DFUR 1,200 mg/day. In two cases of inflammatory breast cancer, the redness of skin was immediately reduced after the first course. After 2 courses, all tumors were decreased over 50% in size. Standard radical mastectomy could be carried out on all patients. Preoperative arterial injection of MIT might be the treatment of choice for locally advanced breast cancer. This preliminary result encourages further study.

DNA content analysis using flow cytometry and amplification of c-myc, L-myc, and c-erbB-2 oncogenes in 143 cases of resected lung cancer were analyzed using the same specimen, and we examined the correlation with prognosis of DNA content and amplification of oncogenes. There were 54 DNA diploid cases (38%), 81 DNA aneuploid cases (57%) and 8 DNA multiploid cases. Analysis of oncogene amplification revealed 22 cases of c-myc, 4 cases of L-myc, and 22 cases of c-erbB-2. In curatively resected cases, the 5-year survival rate was 65% in 31 DNA diploid cases, and 36% in 40 DNA aneuploid cases. There was a statistically significant difference between the two groups (p < 0.02). However, in non-curatively resected cases, the 5-year survival rate was 11% in 23 DNA diploid cases, and 33% in 49 DNA aneuploid cases. There were no statistically significant differences among these groups. The correlation between DNA content and amplification of oncogenes was as follows. In DNA diploid cases, there were 4 cases of c-myc, and 6 cases of c-erbB-2. In DNA aneuploid cases, there were 15 cases of c-myc, 4 cases of L-myc, and 15 cases of c-erbB-2. In DNA multiploid cases, there were 3 cases of c-myc, and 1 cases of c-erbB-2. Amplification of oncogenes was seen more frequently in DNA aneuploid and multiploid cases than in DNA diploid cases. In 71 curative resected cases, the 5-year survival rate for amplified cases of c-myc (10 cases) was 0%, and that of cases with no amplification was 61% (no statistically significant difference). The 5-year survival rate for amplified cases of c-erbB-2 (10 cases) was 40%, against 52% for cases with no amplification. DNA content analysis using flow cytometry was more convenient than analysis of amplification of oncogenes, and reflects the prognosis of resected lung cancer better than oncogenes. There was no relation between DNA content and gene amplification.

Mitoxantrone, a new anti-cancer agent, was successfully prepared for Lipiodol emulsion. The mixture of Mitoxantrone and non-ionic contrast medium, Omnipaque 300, was combined with Lipiodol at the ratio of 1:2. When the ratio of Mitoxantrone and Lipiodol was 1:4, microscopic study revealed stabilized water in oil emulsion, which could release the anti-cancer agent slowly. We applied it for a case of hepatocellular carcinoma with good result. Intra-arterial infusion of this emulsion might be considered effective for treatment of hepatocellular carcinoma.

Changes of the serum tumor marker levels were analyzed in 80 patients with hepatic malignancy treated with chemolipiodolization. In 52 cases, the levels of the tumor marker elevated on the 1st day after treatment with an exponential drop afterwards. The levels of the tumor marker on the first day compared with those before treatment were significantly higher in effectively treated cases. The exponentially declining curve dissociated about 10 days before reaching the lowest point, and it gradually rose again in 32 cases. The second treatment of chemolipiodolization should be applied before dissociation of the exponential curve.