Nobuo Okuyama

Sonodynamic therapy on chemically induced mammary tumor: Pharmacokinetics, tissue distribution and sonodynamically induced antitumor effect of porfimer sodium

The sonodynamically induced antitumor effect of porfimer sodium (PF) was evaluated on a chemically induced mammary tumor in Sprague‐Dawley rats. The timing of 24 h after the administration of PF was chosen for the ultrasonic exposure, based on pharmacokinetic analysis of the PF concentrations in the tumor, plasma, skin and muscle. At a PF dose not less than 2.5 mg/kg and at a free‐field ultrasonic intensity not less than 3 W/cm2, the synergistic effect between PF administration and ultrasonic exposure on the tumor growth inhibition was significant. The ultrasonic intensity showed a relatively sharp threshold for the synergistic antitumor effect, which is typical of an ultrasonic effect mediated by acoustic cavitation. These results suggest that PF is a potentially useful as a sonosensitizer for sonodynamic treatment of chemically induced tumors.

Quantitation of c-erbB-2 Gene Amplification in Breast Cancer Tissue by Competitive PCR

Controversy exists regarding the relationship of the degree of c-erbB-2 amplification to other prognostic factors in breast cancer. To determine the degree of amplification of c-erbB-2 exactly, a sensitive and quantitative method is required. We have developed a competitive PCR method to quantitatively determine the amplification of the c-erbB-2 oncogene. Using this method, we evaluated DNA from 27 breast cancer tissue specimens and DNA from peripheral blood leukocytes from a normal individual. Regarding the relationship between the degree of c-erbB-2 amplification and clinicopathological factors, we found a greater degree of amplification of the c-erbB-2 oncogene in estrogen receptor- negative or progesterone receptor-negative specimens than in positive ones and in lymph node metastasis-positive specimens than in negative specimens, in stages II, III, and IV of disease compared with stage I disease, and in samples with positive lymphatic vessel invasion than with no lymphatic vessel invasion. Generally, these factors were seen in the group of patients who had a bad prognosis. By univariate analysis and multivariate analysis, reverse correlation was observed between amplification of c-erbB-2 and overall survival. Regarding disease-free survival, these relationships were observed only with univariate analysis in our group of patients.

Resection and reconstruction of sternnum

In case of sternal resection, it is necessary to preserve bone material indispensable for the stability of the anterior chest wall and air tightness of the thoracic cavity, and the support of the chest wall integrity must be restored by some means. Various techniques have been applied to the reconstruction of the chest wall following resection. During the last 10 years, we have performed reconstructive operation for 6 cases of the chest wall following resection of the sternum in recurrent cases of breast cancer or invaded case of primary breast cancer. In these patients, the chest wall was reconstructed using a rib-latissimus dorsi osteomyocutaneolus flap or a latissimus dorsi myocutaneous flap. The sternum was totally resected in 3 cases, and in all 3 cases, reconstructed using a rib-latissimus dorsi osteomyocutaneous flap. Although postoperative pulmonary function decreased, all cases could be relieved from endotracheal intubation within 17 hours after operation, and had no problems in activities of daily living or occurrence of chest flailing or paradoxical movement of the chest. An artificial material (expanded polytetrafluoroethlene patch) was used in only one patient for the reconstruction of the osseous thorax, but this case developed infection during postoperative chemotherapy. After this experience, we used only biological materials for the reconstruction of the chest wall and postoperatively performed radiotherapy and/or chemotherapy on all cases. We have observed no flap infection or detachment since then. One characteristic of using the latissimus dorsi myocutaneous flap is that it is easily elevated and rarely causes serious postoperative esthetic or functional problems. The flap is also easily utilized to reinforce the osseous thorax because ribs immediately below the latissimus dorsi muscle are readily mobilized as a pedicle graft. Reconstruction of the chest wall following resection of the sternum, described in this report, allowed us to perform radiotherapy and/or chemotherapy without serious postoperative complications on the cases relapsing after treatment of breast cancer. The 2-year survival rate is 50% and one of these cases survived up to 10 years after resection of the sternum. Thus we prefer to perform resection of the sternum for sternal recurrence of breast cancer if there are no metastatic lesions in other organs.

Adenomyoepithelioma of the breast: a case report and a review of the literature

A 74-year-old woman complained of a small nodule in the outer lower quadrant of her left breast. On physical examination, a 0.9 × 0.8 cm, round-shaped and firmly elastic nodule was palpated.Excisional biopsy was performed. Histologically, the tumor was separated into, with a bicellular pattern, containing both numerous glandular structures and numerous spindle-shaped cells.Immunohistochemical staining for EMA and cytokeratin showed strongly positive immunoreactivity for epithelial cells. Staining for α-SMA showed strongly positive immunoreactivity for myoepithelial components. Staining for keratin and S-100 protein showed weakly positive immunoreactivity for myoepithelial cells. Microscopically, the tumor was diagnosed as adenomyoepithelioma of the breast.Immunohistochemical examination is needed to distinguish epithelial cell proliferation from myoepithelial cell proliferation.Immunohistochemical examination using antibodies against EMA, α-SMA, keratin, cytokeratin and S-100 protein, is indispensable.

Efficacy of doxifluridine combined with weekly paclitaxel therapy in the treatment of advanced or recurrent breast cancer: results of the JMTO BC01 phase II trial.

We conducted a phase II study to determine the availability and safety of combination chemotherapy with weekly paclitaxel and doxifluridine (a capecitabine metabolite) in the treatment of advanced or recurrent breast cancer. Patients were treated with a combination chemotherapy regimen: doxifluridine was orally administered at 800 mg/day for 14 days, followed by a 7-day washout period. Paclitaxel was given intravenously on days 1 and 8 at 80 mg/m2 for 1 h, followed by a 1-week washout period. This 3-week cycle of therapy was repeated as long as possible (at least eight cycles) until the progression of the tumor and drug-related adverse effects were no longer observed. From May 2003 to December 2005, 26 patients were enrolled in the study. The overall response rate was 53.8% (95% confidence interval, 33.4–73.4%). The clinical benefit rate, including long-term no change, was 65.4% (95% confidence interval, 44.3–82.8%). Time to progression and survival time were 297 and 1182 days, respectively, for the 26 enrolled patients. No severe toxicities were observed. Grade 3/4 leucopenia in three patients, neutropenia in five patients, increased serum creatinine in three patients, hypercalemia in one patient, hypocalcemia in one patient, nausea/vomiting in two patients, and diarrhea in one patient. The good response rate and long time to progression and overall survival time of this doxifluridine combined with weekly paclitaxel therapy indicate its potential as a first-line or second-line treatment for advanced or recurrent breast cancer patients.