Health-related quality of life,psychological distress,and adverse events in postmenopausal women with breast cancer who receive tamoxifen,exemestane, or anastrozole as adjuvant endocrine therapy: National Surgical Adjuvant Study of Breast Cancer 04 (N-SAS BC 04)

Health-related quality of life (HRQOL), symptoms of depression, and adverse events (AEs) were compared between Japanese postmenopausal patients with hormone-sensitive breast cancer (BC) who received adjuvant tamoxifen, exemestane, or anastrozole in an open-labeled, randomized, multicenter trial designated as the National Surgical Adjuvant Study of Breast Cancer (N-SAS BC) 04 substudy of the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial. During the first year of treatment, HRQOL and symptoms of depression were analyzed using the Functional Assessment of Cancer Therapy-Breast (FACT-B) and its Endocrine Symptom Subscale (ES), and the Center for Epidemiologic Studies Depression Scale (CES-D), respectively. In addition, predefined AEs were analyzed. A total of 166 eligible patients were randomly assigned to receive adjuvant tamoxifen, exemestane, or anastrozole. FACT-B scores increased after treatment began and remained significantly higher in the tamoxifen group than in the exemestane group or anastrozole group during the first year (P = 0.045). FACT-B scores were similar in the exemestane group and anastrozole group. ES scores and CES-D scores were similar in all treatment groups. Arthralgia and fatigue were less frequent, but vaginal discharge was more frequent in the tamoxifen group than in the exemestane group or anastrozole group. HRQOL was better in Japanese postmenopausal women treated with tamoxifen than those treated with exemestane or anastrozole. HRQOL and AEs were similar with exemestane and anastrozole. Given the results of the TEAM trial, upfront use of tamoxifen followed by an aromatase inhibitor (AI) may be an important option for adjuvant endocrine therapy in Japanese postmenopausal women.     

Current trends of sentinel lymph node biopsy for breast cancer —A surgeon’s perspective

Sentinel lymph node biopsy (SLNB) is standard care for patients with early-stage breast cancer, and axillary lymph node dissection (ALND) is considered unnecessary when sentinel lymph nodes (SLNs) are tumor-free. Additional non-SLN metastasis in patients with positive SLNs can be estimated using several risk factors such as primary tumor size, metastatic tumor size in SLNs, lymphatic vessel invasion, and so on. All patients with positive SLNs may be treated with further ALND based on their own risk for nonSLN metastasis. Recent randomized clinical trials have already proved less surgical morbidity and better QOL for SLNB alone compared with ALND. However, trials concerning the efficacy of ALND in positive SLNB patients in preventing local regional recurrence and improving overall survival compared with no ALND, and also, concerning the effectiveness of ALND compared with axillary radiation therapy (RT), have not yielded clear results. The prognostic significance of micrometastasis in SLNs or bone marrow also remains to be determined. So far SLNB is not acceptable for patients with positive nodes in the axilla at initial diagnosis even if their axillary metastases are down-staged to negative by neoadjuvant chemotherapy. Although basically SLNB does not need to be performed for patients with pure ductal carcinoma in situ (DCIS), it is recommended for patients with an initial diagnosis of DCIS which is large, palpable, high grade, or found in younger patients. Because these types of DCIS have higher incidences of accompanying invasive lesions. In addition if patients will undergo mastectomy, SLNB is recommended because of the inability to perform SLNB after mastectomy. SLNB may be acceptable for patients with T3 or T4b tumors, even though SLN identification is lower yet SLN involvement is higher compared with T1 or T2 tumors, and systemic adjuvant therapy is more important for patients with T3 or T4b tumors. SLNB is a bridge to further axillary treatment such as ALND or axillary RT, and which strategy, including no further treatment, is best considered individually based on recurrence risk, treatment responsiveness and use or non-use of systemic therapy.     

Gelatin-resorcinol-formaldehyde-glutaraldehyde glue for sealing pulmonary air leaks during thoracoscopic operation

BACKGROUND: Intraoperative pulmonary air leakage is one of the most troublesome complications in video-assisted thoracoscopic surgical procedures. We developed a sealing procedure using gelatin-resorcinol-formaldehyde-glutaraldehyde (GRFG) glue for pulmonary air leaks during such operations. METHODS: Formaldehyde-glutaraldehyde (FG) jelly is prepared by mixing FG fluid with 2.5% sodium carboxymethyl cellulose to make the FG fluid viscous. We performed an adhesion-strength test to determine the optimum ratio of gelatin-resorcinol mixture to FG jelly and then conducted an air leakage test on swine lung to compare the sealing effect between fibrin and GRFG glues. To study the histotoxicity of the GRFG glue, the sealant was applied to injured rabbit lung, and the rabbits were followed for 1 day to 188 days. For clinical studies, we developed an endosyringe to apply the GRFG glue on the target site during video-assisted thoracoscopic surgical procedures and used this technique in 21 patients with intraoperative air leaks. In addition, the side effects of GRFG glue application were studied in 52 patients in whom glue was used in several ways during lung operations. RESULTS: The results of the adhesion-strength test favored a 2:1 gelatin-resorcinol to FG ratio. The mean pressure required to produce air leakage was significantly higher with GRFG glue than with fibrin glue (p<0.001). No critical histologic damage was seen in the rabbit lung, and the glue persisted on the lung surface for 188 days after sealing. Clinical application of the glue in 21 patients resulted in complete stoppage of air leakage during operation and long afterward, except in 1 patient with a late-onset lung fistula. The FG jelly helped prevent glue spillage at the target site, regardless of angle. A transient rise in temperature up to 38.60C was observed as a side effect 7 days after operation in 5 (9.6%) of the 52 patients. CONCLUSIONS: A GRFG glue using FG jelly seals pulmonary air leaks effectively, simply, and safely during video-assisted thoracoscopic surgical procedures.     

Enhancement of immunohistochemical reactivity for thymidine phosphorylase in breast carcinoma cells after administration of docetaxel as a neoadjuvant chemotherapy in advanced breast cancer patients

For the purpose of demonstrating possible effects of docetaxel on thymidine phosphorylase (TP) activity in human breast carcinoma, we examined breast carcinoma tissues pre- and post-administration of docetaxel, by an immunohistochemical method using an anti-TP monoclonal antibody. Eight patients with advanced breast carcinoma were initially treated with 3 cycles of 60 mg/m2 of docetaxel once every 3 weeks after incisional biopsy of tumors, and following 3 cycles of docetaxel, they underwent mastectomy with axillary dissection. Grades of immunohistochemical reactivity for TP of carcinoma cells in pre- and post-treatment specimens were compared. Five biopsy specimens (62.5%) were positive for TP. After administration of docetaxel, 6 of 8 cases (75.0%) revealed significant enhancement of reactivity for TP. Increased reactivity was recognized diffusely as well as focally in carcinoma tissues. From these results, we believe that administration of docetaxel to breast cancer patients evokes enhancement of immunohistochemical reactivity for TP in breast carcinoma cells in situ. Furthermore, we consider that docetaxel treatment might improve efficacy of additional doxifluridine and capecitabine therapy.     

Long-term results of breast-conserving treatment for early-stage breast cancer in Japanese women from multicenter investigation

BACKGROUND: Although many clinical data regarding breast-conserving treatment have already been reported from European and North American countries, few clinical data with long-term follow-up have been reported from Japan. METHOD: We collected information on therapeutic and possible or developed prognostic factors and follow-up data for Japanese women who had received breast-conserving treatment consisting of wide excision of the primary tumor, axillary dissection and radiotherapy for unilateral breast cancer considered suitable for breast-conserving treatment from 18 Japanese major breast cancer treating hospitals; 1561 patients were registered. RESULTS: The median follow-up period was 77 months. Five-year disease-free and overall survival rates were 89.4 and 95.9%, respectively. The 5-year local recurrence-free rate was 96.3%. The patients with histologically positive margins (P < 0.0001) or estrogen receptor negative tumor (P = 0.0340) or younger than 40 years old (P < 0.0001) developed statistically significantly more local recurrences. Adjuvant endocrine therapy was essential for the estrogen receptor positive patients to have a lower local recurrence rate. Endocrine therapy did not change the local recurrence rate among estrogen receptor negative patients at all. Multivariate analysis showed histological margin status and the combination of estrogen receptor status and endocrine therapy were independent prognostic factors for local recurrence. CONCLUSION: The 5-year local recurrence rate of Japanese breast cancer patients who were treated with breast-conserving treatment using radiotherapy was 3.7%. Independent prognostic factors for local recurrence were histological margin status and the combination of estrogen receptor status and adjuvant endocrine therapy.     

Radiological examination for peripheral lung cancers and benign nodules less than 10 mm

To clarify the differences in radiological findings between primary lung cancers and benign nodules measuring less than 10mm, we examined chest computed tomography (CT) findings. Of 82 patients with solitary pulmonary nodules less than 10mm in diameter who had undergone surgical biopsy, 21 patients with primary lung cancer and 45 patients with benign lesions (9 patients with tuberculosis, 12 with non-specific inflammation, 10 with benign lung tumor, 10 with intrapulmonary lymph nodes and 4 with others) were examined. Seven patients with atypical adenomatous hyperplasia and nine patients with metastatic lung cancer were excluded. Primary lung cancers had an ill-defined tumor margin and spiculation significantly more frequently than benign nodules (P<0.01). Involvement of bronchi or vessels was observed significantly more frequently in primary lung cancers than in benign nodules (P<0.05), while pleural indentation did not show significant differences in frequency. Retrospective chest X-ray or CT films were reviewed for seven patients with primary lung cancers and 12 with benign nodules, with a mean interval of 24+/-17 months. Primary lung cancers enlarged or appeared as new nodules more frequently than benign lung nodules (P<0.05). Among 17 lung cancer patients who underwent mediastinal lymph node dissection, the cancer was at a more advanced stage than T1N0M0 in four (24%). We conclude that ill-defined margins, spiculation, involvement of bronchi or vessels, and tumor enlargement visualized by CT are still important signs of malignancy even for nodules less than 10mm in size. Tumor size, even for lung cancers measuring less than 10mm, is not an indication for limited resection.     

The relationship of placement accuracy and insertion times for the laryngeal mask airway to the training of inexperienced dental students

Any health care professional can be faced with a medical emergency in which the patient needs ventilatory support. Bag-valve-mask ventilation with the assistance of an oropharyngeal airway that uses 100% oxygen is currently the preferred method for artificial ventilation. This procedure is generally performed ineffectively by most dentists inexperienced in airway management. We examined whether a short and simple period of training by dental students inexperienced in airway management would increase the speed and accuracy of the placement of the laryngeal mask airway (LMA), which may be a superior airway device to the bag-valve-mask and oropharyngeal airway. Thirty-five dental students inexperienced in airway management were divided into 3 groups. The first group received only a demonstration on how to use the LMA. The second and third groups received the demonstration plus practiced inserting the LMA 5 and 10 times, respectively. A dental anesthesiologist graded the placement of the LMA with a tracheobroncho-fiberscope (fiberoptic bronchoscope). Those who practiced inserting the LMA 5 times faired better than those who received no training; however, those who practiced 10 times did not do any better than the second group. The LMA can be inserted rapidly and effectively by dentists inexperienced in airway management after a short period of simple training that may be critical when personnel experienced in intubation are not readily available.     

The efficacy and side effects of gelatin-resorcinol formaldehyde-glutaraldehyde (GRFG) glue for preventing and sealing pulmonary air leakage

(Received for publication on Jan. 5, 1999; accepted on Sept. 17, 1999)     

T-zone histiocytes in adenocarcinoma of the lung in relation to postoperative prognosis

Infiltration of T-zone histiocytes (Langerhans' cells and their precursors) and macrophages was investigated by immunohistochemical methods with the use of anti-S100 protein and anti-lysozyme antibodies in 40 Stage Ia cases of adenocarcinoma of the lung. Varying population densities of S100+ T-zone histiocytes were demonstrated in 31 (77.5%) of 40 adenocarcinomas; however, lysozyme+ macrophages were found in almost equal quantities in all cases of adenocarcinoma. The distribution of T-zone histiocytes was clearly different from that of macrophages. Namely, the former was mainly interspersed among the tumor cells, whereas macrophages were found in the stroma and around necrotic foci. The prognosis of Stage Ia adenocarcinoma cases was related to the density of T-zone histiocytes in tumor tissues. Patients with marked infiltration of T-zone histiocytes survived longer than those without or with only slight infiltration (P less than 0.05). Such relationship was not observed with regard to macrophages. This indicates that T-zone histiocytes infiltrating within the tumor and regional lymph nodes may play a role in host defense mechanisms against tumor in the early stage of adenocarcinoma of the lung.     

Immunomorphologic responses of regional lymph nodes and prognosis in patients with stage Ia pulmonary adenocarcinoma

The relationship between postoperative prognosis and the immunomorphologic response of regional lymph nodes was examined in 50 patients with stage Ia peripheral bronchial adenocarcinoma and compared with 22 patients in stage Ib and II. Regarding paracortical lymphocyte hyperplasia, the prognosis of the responsive group in patients with stage Ia was significantly better than that of the non-responsive group; however, no definite relationship was found between follicular hyperplasia and prognosis. Follicular hyperplasia correlated with the size of the primary lesion or the distance from the site of the primary lesion. In stage Ib and II cases with metastasis to the pulmonary hilar lymph nodes, paracortical lymphocyte hyperplasia or follicular hyperplasia had no relation to the postoperative prognosis.