The effect of exemestane, anastrozole, and tamoxifen on lipid profiles in Japanese postmenopausal early breast cancer patients: final results of National Surgical Adjuvant Study BC 04, the TEAM Japan sub-study.

BACKGROUND: In this Tamoxifen Exemestane Adjuvant Multinational Japan sub-study, we evaluated the time course of changes in serum lipids in postmenopausal women with hormone-sensitive early breast cancer treated with exemestane, anastrozole, or tamoxifen for postoperative adjuvant therapy. PATIENTS AND METHODS: A total of 154 breast cancer patients were assigned to receive exemestane, anastrozole, or tamoxifen in this randomized open-label study. Serum lipid parameters including triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were measured during 1 year of treatment. RESULTS: TC and LDL-C rapidly decreased in patients treated with tamoxifen at 3 months. Compared with anastrozole and exemestane patients, TC and LDL-C were significantly lower at all assessment time points in tamoxifen patients (P < 0.05). TG increased in tamoxifen patients; it was significantly higher compared with exemestane patients at all assessment time points (P < 0.05). HDL-C slightly decreased in exemestane patients; it was significantly lower compared with anastrozole patients at 3 months and 1 year (P = 0.0179 and 0.0013, respectively). CONCLUSION: Changes of lipid profiles in Japanese postmenopausal women treated with tamoxifen were relatively favorable, while exemestane and anastrozole had no clinically significant effect on the serum lipids.

Effects of exemestane, anastrozole and tamoxifen on bone mineral density and bone turnover markers in postmenopausal early breast cancer patients: results of N-SAS BC 04, the TEAM Japan substudy.

BACKGROUND: Use of aromatase inhibitors in women with postmenopausal breast cancer accompanies risks of bone loss. We evaluated changes in bone mineral density (BMD) and bone turnover markers in patients treated with exemestane, anastrozole or tamoxifen for hormone-sensitive postmenopausal early breast cancer. PATIENTS AND METHODS: Sixty-eight patients enrolled in the Tamoxifen Exemestane Adjuvant Multinational Japan bone substudy were randomly assigned to receive tamoxifen, exemestane or anastrozole. During a 2-year study period, lumbar spine BMD was measured using dual-energy X-ray absorptiometry, and urinary type I collagen cross-linked N-telopeptide (NTX) and serum bone-specific alkaline phosphatase (BAP) were also measured. RESULTS: BMD at 2 years of treatment was higher in tamoxifen patients compared with exemestane and anastrozole patients; however, the intergroup difference was not significant (p = 0.2521 and p = 0.0753, respectively). BMD was higher in exemestane patients compared with anastrozole patients; however, the intergroup difference was not significant (p = 0.7059 and p = 0.8134, respectively). NTX and BAP were significantly lower in tamoxifen patients compared with exemestane and anastrozole patients at 1 and 2 years of treatment (p < 0.05). CONCLUSION: Tamoxifen may provide better bone protection compared with exemestane or anastrozole. The effect of exemestane and anastrozole on bone loss may be comparable in Japanese postmenopausal women.

[Is video-assisted thoracic surgery lobectomy better than minimally invasive open thoracotomy?].

This article reviews our experiences of the current video-assisted thoracic surgery (VATS) lobectomy and minimally invasive open thoracotomy for resection of lung cancer. Between August 1999 and April 2007 at Saiseikai Central Hospital, Tokyo, Japan, we performed VATS lobectomy in 243 patients with clinical stage I lung cancer. It is certain that VATS lobectomy is acceptable in view of its low invasiveness, mortality, morbidity. And from an oncological viewpoint, VATS lobectomy is not inferior to conventional lobectomy. Therefore, we consider VATS lobectomy to be one of the therapeutic options in patients with clinical stage I lung cancer. However, what is most important is to achieve an anatomic lobectomy and complete mediastinal lymph node dissection. It may be that it is not important for differences of approach methods.

[Lipoma of the diaphragm; report of a case].

A 50-year-old man was referred to our hospital with an abnormal shadow on chest roentgenogram taken on a health examination in September, 1999. His past history was an operation for scoliosis at the age of 39 years. His family history was unremarkable. Chest roentgenogram showed a smooth rounded bulging nodule in continuity with the left diaphragm. Chest computed tomography (CT) revealed a well-defined and homogeneous nodular lesion with a low attenuation value of -100 Hounsfield unit, corresponding with a fat density, on the base of the left hemithorax. For making diagnosis and treatment, videothoracoscopic surgery was performed in January, 2000. The tumor was removed with combined resection of diaphragm, using stapling device, because the lesion partially adhered to the diaphragm. The postoperative course was uneventful. The pathological diagnosis was lipoma About 2 years later. he was again found to have a similar abnormal shadow on a routine chest roentgenogram in August, 2003. Chest CT showed a nodular lesion involving a previous operative staple line on the base of the left hemithorax. We considered this lesion to be a locally recurrent tumor and performed surgical resection of the lesion with a wide margin of normal diaphragm and partial retroperitoneal fat tissue. The pathological diagnosis of the resected specimen was again lipoma. Since then, he has been in good health without recurrence for about 4 years.

Randomized trial of cyclophosphamide, doxorubicin, and vincristine versus cisplatin and etoposide versus alternation of these regimens in small-cell lung cancer.

Between April 1985 and May 1988, we conducted a randomized study comparing two standard chemotherapy regimens with the same regimens given on an alternating basis in patients with small-cell lung cancer. The patients were randomly assigned to receive cyclophosphamide at a dose of 800 mg/m2 intravenously (IV) on day 1, doxorubicin at 50 mg/m2 IV on day 1, and vincristine at 1.4 mg/m2 IV on day 1 (CAV); cisplatin at 80 mg/m2 IV on day 1 and etoposide at 100 mg/m2 IV on days 1, 3, and 5 (PE); or CAV alternating with PE (CAV/PE). Each regimen was repeated every 3-4 weeks. Three hundred patients were entered in the study, and 288 of them were eligible for analysis (97 for CAV, 97 for PE, and 94 for CAV/PE). The response rates for PE (78%) and CAV/PE (76%) were significantly higher than the rate for CAV (55%), while the complete response rates were similar (14%, 16%, and 15%, respectively). Nine (23%) of 39 patients who failed to respond to the initial CAV regimen responded to PE when they were crossed over. In contrast, only one (8%) of 13 patients responded to CAV after failing to respond to the PE regimen, suggesting that these two regimens were partially non-cross-resistant. The response duration on CAV/PE was significantly longer than that with CAV (P = .004). The survival time with CAV/PE (11.8 months) was superior to that with CAV (9.9 months) (P = .027) or that with PE (9.9 months) (P = .056). In patients with limited disease, the survival in the alternating arm was significantly superior to the survival in the CAV arm (P = .014) or the survival in the PE arm (P = .023). The toxic effects were acceptable in all three chemotherapy regimens. These results favor the alternating chemotherapy over either standard chemotherapy, such as CAV and PE, although the differences are not dramatic.

Multiple primary cancers in 5,456 autopsy cases in the National Cancer Center of Japan.

Multiple primary malignant neoplasms in 5,456 consecutive autopsy cases from 1962 to 1981 in the National Cancer Center were analyzed. There were 285 (5.2%) double primary cancers, 58 (1.1%) triple or more, and 65 (1.2%) minute cancers of the thyroid or prostate gland. Higher incidence of second cancer is observed in cancers of the oropharynx, intestine, larynx, uterus, bladder, and thyroid. Organ association between the two cancers was present in certain organs; for example, there was a tendency for upper gastrointestinal tract cancers to be associated with lower gastrointestinal tract cancers. Influence of histologic subtypes in multiple cancer cases is discussed for lung cancer.

Association of CYP1B1 genetic polymorphism with incidence to breast and lung cancer.

Cytochrome P450 1B1 (CYP1B1) participates in the metabolic activation of a number of procarcinogens including benzo[a]pyrene and the hydroxylation of 17beta-estradiol at the C-4 position. In this study, we investigated the association between CYP1B1 genetic polymorphism and breast or lung cancer incidence. The Ala-Ser polymorphism at codon 119 in presumed substrate recognition site 1 was significantly associated with the incidence of breast or squamous cell carcinoma of the lung. On the other hand, Leu-Val polymorphism at codon 432 did not show any association to the cancers. An allele containing both Ala and Leu simultaneously, comprised 75% of alleles among 315 Japanese healthy controls, was significantly inversely associated with breast cancer incidence. When expressed in a recombinant system, this CYP1B1 cDNA showed the lowest 17beta-estradiol 4-hydroxylase activity among four different variant forms of CYP1B1. Thus, inter-individual differences in activation of procarcinogens or metabolism of oestrogen originating from genetic polymorphisms of the human CYP1B1 gene may contribute to the susceptibility of human cancers.

Squamous cell carcinoma of the thymus. An analysis of eight cases.

Eight cases of squamous cell carcinoma of the anterior mediastinum, most likely derived from the thymus, are presented. Seven were male and one female ranging in age from 39 to 65 years; the average was 55.5 years. There were no cases associated with any paraneoplastic syndromes. They possessed common morphological characteristics. Grossly, the tumors resembled malignant thymoma. Invasion of the lung and metastases to regional lymph nodes were frequent. Often observed microscopically were foci of sharply defined keratinization resembling Hassall's corpuscles, no radial arrangement of tumor cells at the periphery of nests, and broad, fibrotic, or hyalinized stroma. Admixture of a few lymphoid cells and some features transitional to thymoma were also observed in some parts of tumors. However, undoubtedly carcinomatous areas were present in some or large parts of all the tumors, where individual cells possessed a vesicular nucleus and a prominent round nucleolus. These features were distinct from those of bronchogenic squamous cell carcinoma and other thymic tumors, although they appeared to be related to thymoma. Treatment of choice is radical surgery and postoperative radiotherapy, because of relatively high radiosensitivity. Prognosis of patients was relatively good. From analyses of cases it is concluded that squamous cell carcinoma of the thymus should be separated from ordinary thymoma of the epithelial type, and that squamous cell carcinoma involving both the thymus and lungs should be carefully examined for the primary site of growth.

Expression of vimentin in surgically resected adenocarcinomas and large cell carcinomas of lung.

The expression of vimentin in pulmonary carcinomas was studied in 285 cases of surgically resected lung cancer from our hospital files. Formalin fixed, paraffin-embedded sections were studied by immunoreactive staining techniques using two monoclonal antibodies against vimentin. Cases demonstrating vimentin positivity by the avidin-biotin-peroxidase method included 11 of 129 adenocarcinomas studied (8.5%), and 15 of 61 large cell carcinomas studied (24.6%). Vimentin expression was not seen in any of the 51 squamous cell carcinomas or 35 small cell carcinomas in our series. The positive cases of adenocarcinoma were in moderately and poorly differentiated cancers. Four of the eight giant cell carcinomas (50%) demonstrated vimentin expression. All cases that exhibited vimentin positivity were studied for cytokeratin expression. Coexpression of vimentin and cytokeratin was demonstrated not only within the same tumor but also within the same cells in some cases stained by double antibody technique, including both adenocarcinomas and large cell carcinomas. Similar immunoreactive methods were also applied to sections from human lung cancer transplants grown in the nude mouse. Of 28 tumors studied, four of 11 adenocarcinomas (36%) and all 4 large cell carcinomas demonstrated coexpression of vimentin and cytokeratin, while none of the five squamous cell carcinomas or eight small cell carcinomas expressed vimentin.

Biological, pathological and clinical features of small cell lung cancer.

Small cell lung cancer, which is not uncommon, and is one of the most malignant and relatively well investigated solid tumors of adults, has been reviewed concerning its biology, pathology and clinical aspects. Although it is histologically very simple, its poorly differentiated epithelial cell characteristics are complicated by features of neuroendocrine cells, such as amine and peptide hormone production and specific enzyme activities, some of which have been found to be good monitoring markers during and after treatment. Because of the relative ease of establishing cell lines in vitro, cell characteristics have been studied in detail. This has led to subtyping of cell lines and may further lead to subtyping of histology. However, accumulation of further evidence has disclosed exceptions and unclassifiable cell lines. The same can be said about chromosomal abnormality. The reactivity of monoclonal antibodies and also oncogenes supports the prevalent concept discriminating small cell cancer from non-small cell cancer. However, concepts concerning histogenesis are still changing. Although it is one of the solid tumors most sensitive to radiation and chemotherapy, the response rate of the tumor to non-surgical treatment appears to have reached a plateau. In order to make a breakthrough in the treatment, strategies based on biological findings must be applied.

Granulocyte colony-stimulating factor-producing primary pericardial mesothelioma.

A 54-year-old male patient presented with a granulocyte colony-stimulating factor (G-CSF)-producing primary pericardial mesothelioma, while showing symptoms of congestive heart failure, a fever of 38 to 39 degrees C, and marked leucocytosis of 52.7 x 10(3) cells/mm3. The histopathologic diagnosis was established after autopsy. G-CSF production was confirmed by the expression of G-CSF mRNA in the tumor extract and the patient's high serum G-CSF concentration. The expression of G-CSF by benign and malignant mesothelial cells has already been reported. However, this is the first case report of G-CSF production in a pericardial mesothelioma.

Dumon stent placement via endotracheal tube.

BACKGROUND: Dumon stent placement requires use of a technically difficult rigid bronchoscope. A recently developed technique for placing a Dumon stent introduced via a conventional endotracheal tube is detailed herein. METHODS: The conventional endotracheal tube is inserted beyond the stenosis site; this procedure is observed with the use of a flexible bronchoscope with the patient undergoing general anesthesia. The Dumon stent is folded and inserted into the endotracheal tube and is introduced into the stenosis site with the use of a cylindrical-tipped stainless steel wire as a pusher. The endotracheal tube is withdrawn while the pusher is positioned to expand the stent at the stenosis site. Dumon stents of 12 to 16 mm in diameter were put in place using the present method in 5 cases of tracheobronchial stenosis. RESULTS: The mean time from endotracheal tube insertion to stent placement was 181 s. The present method positioned the Dumon stent more easily and safely than the original rigid bronchoscope because the endotracheal tube used was flexible. One patient, however, required a tracheostomy and surgical forceps to remove the stent 3 months after placement. CONCLUSION: While Dumon stent removal may require a rigid bronchoscope or tracheostomy, stents can be introduced without difficulty via a conventional endotracheal tube.

Anterior limited thoracotomy with intrathoracic illumination for lung cancer: its advantages over anteroaxillary and posterolateral thoracotomy.

STUDY OBJECTIVE: We developed anterior limited thoracotomy (ALT) with intrathoracic illumination for curative resection of lung cancer. The present study evaluated the benefits of ALT by retrospective comparison with anteroaxillary thoracotomy (AAT) and posterolateral thoracotomy (PLT). DESIGN: Lung cancer patients, who underwent lobectomy via ALT (n = 28), AAT (n = 28), and PLT (n = 28), were matched by gender and age. Operating time, blood loss during operation, chest tube drainage volume 24 h after surgery, chest tube drainage duration, and vital capacity (VC) and chest pain from early to late postoperative period were studied for ALT, AAT, and PLT. Early postoperative chest pain was evaluated by a visual analog scale and analgesic requirements, and chronic pain was divided into five grades. RESULTS: No difference was observed in operating time among ALT, AAT, and PLT. ALT has the following advantages over PLT: (1) less blood loss during surgery (p < 0.05); (2) reduced postoperative drainage volume (p < 0.05) resulting in shorter chest tube drainage (p < 0.001); (3) diminished impairment of VC for 1 week to 6 months after surgery (p < 0.01 or p < 0.001); and (4) reduced pain from 1 day and 6 months after surgery (p < 0.001). ALT also has the advantage over AAT in reduced pain 5 days (p < 0.01) and 7 days (p < 0.05) after surgery and in decreased analgesic requirements during 14 days after surgery (p < 0.05). CONCLUSION: ALT is a sufficient and minimally invasive thoracotomy alternative to PLT or AAT for curative lung cancer resection.

Surgical treatment for lung cancer with metastasis to mediastinal lymph nodes.

A series of cases of lung cancer were analyzed, with particular attention to the relationship between the presence of lymph node metastases and the prognosis for surgical intervention. The cases are classified into four clinical stages and a detailed classification of histologically proved lymph node metastasis and pleural involvement is presented. Results indicate that the presence of mediastinal lymph node metastasis, especially in cases with squamous-cell carcinoma and negative subcarinal lymph node, does not contraindicate surgical treatment.

Lymph node mapping and curability at various levels of metastasis in resected lung cancer.

By means of lymph mapping, the prognosis significance of lymph node metastasis in lung cancer was studied in 270 patients who had undergone radical operations--pulmonary resection combined with complete mediastinal lymph node disection, which is used for patients in whom all cancer could thereby be ablated. Mediastinal lymph node metastasis was found in 64 patients, and 12 patients lived 5 years or more (an absolute 5 year survival rate of 18.8 percent). After radical surgery, there was a significant difference between the prognosis for patients who had metastases to the subcrainal lymph nodes as compared to the prognosis for those who did not. The 5 years survival rates were 9.1 percent and 29.0 percent, respectively. On the other hand, prognosis was not significantly affected by involvement or noninvolvement of the superior mediastinal, paratracheal, tracheobronchial, pretracheal, and the subaortic and para-aortic lymph nodes. No significant difference in survival was detected between patients who were given adjuvant therapy and those who were not. Lymph node mapping gives valuable prognostic information.

Thoracic duct cyst of the mediastinum.

A case of mediastinal thoracic duct cyst is described. It is believed to be the first to be diagnosed before thoracotomy. Seven surgically treated cases have been reported but in none was the diagnosis made before operation. This case report concerns a 49-year-old woman who was operated upon because of a thoracic duct cyst that had been diagnosed by lymphangiography before the operation. Symptoms were caused by pressure of the cyst on the esophagus. The operation and immediate postoperative course were uneventful. One year later, the patient was doing well and no further investigation was recommended.

Prognosis and survival in resected lung carcinoma based on the new international staging system.

A new TNM staging system was proposed and the previous system has been revised recently. To evaluate the new TNM staging system for lung cancer, we analyzed records of 1737 patients who underwent pulmonary resection at the National Cancer Center Hospital, Tokyo. With regard to clinical stages, three patients had occult carcinoma; 821 patients had stage I disease; 248 patients, stage II; 465 patients, stage IIIA; 82 patients, stage IIIB; and 118 patients, stage IV. The 5-year survival rates for the respective stages were 50.1% for stage I, 31.2% for stage II, 20.2% for stage IIIA, 5.1% for stage IIIB, and 7.9% for stage IV. In terms of postoperative stages, four patients were classified in stage 0, 536 in stage I, 221 in stage II, 559 in stage IIIA, 159 in stage IIIB, and 258 in stage IV. The 5-year survival rates were as follows: stage I, 65.0%; stage II, 42.9%; stage IIIA, 22.2%; stage IIIB, 5.6%; and stage IV, 7.5%. In both the clinical stage and the postoperative stage, there were significant prognostic differences between stage I and stage II, stage II and stage IIIA, and stage IIIA and stage IIIB, but there was no significant difference in 5-year survival rates between stage IIIB and stage IV.

Resection of tracheal carina for lung cancer. Procedure, complications, and mortality.

We studied 20 patients with lung cancer that invaded the tracheal carina who were operated on during a recent 12-year period. Fifteen patients underwent sleeve pneumonectomy, two had pneumonectomy, one had lobectomy with wedge resection of the carina, and two patients had sleeve resection of the carina followed by reconstruction of the carina. There were two patients with postsurgical stage IIIA lung cancer, 15 with stage IIIB, and three with stage IV disease that involved intrapulmonary metastases. However, the operations of 13 patients were curative resections in which the surgical margin was negative for disease. Sleeve pneumonectomy was performed only in the last 3 years of the study period, after we had confirmed the safety and good results of bronchoplastic surgery by our experience of 100 cases of sleeve lobectomy. Hence, the period of follow-up in this group is too short to assess long-term survival. Eleven patients are alive, three died within 1 month after operation (15%), three died in the hospital beyond 1 month after the operation, and three died after discharge from hospital. Nine of the 11 surviving patients have no evidence of disease 1 month to 2 1/2 years after the operation, but two are alive with supraclavicular lymph node metastases. The 1-year and 2-year survival rates for 17 cases (excluding the three operative deaths) were both 59% by the Kaplan-Meier method. Two different methods were used to adjust the difference of calibers of the trachea and the bronchus. The first method involved the shift of the edge of the cartilagonous portion of the bronchus against the edge of the cartilaginous portion of the trachea and the other involved cutting the tracheal wall as a wedge-shaped piece to shorten the diameter of the tracheal caliber. To prevent complications after resection of the tracheal carina in 11 recent cases with sleeve pneumonectomy, anastomoses were protected by a pedicle fat flap nourished by internal thoracic artery and vein. No postoperative complications of anastomoses developed in any of these cases.

Bronchoplastic procedures for lung cancer.

Twenty patients with lung cancer have undergone bronchoplastic procedures September, 1965, to June, 1976 in our hospital. Bronchoplastic procedures are considered to be indicated for early cases of hilar lung cancer rather than for somewhat advanced cases. Endoscopic examination and roentgenograms of the bronchial arteries are needed to delineate resectional lines of bronchus, the former for deciding the mucosal extent and the latter the intrabronchial extent of the tumor. The bronchoplastic procedures we adopted were free from the risks and dangers generally accompanying the operation, and there were no postoperative deaths. For the prevention of postoperative complications, careful attention to suture technique is needed, and postoperative bronchoscopic suction of intrabronchial secretions is absolutely necessary. These procedures assure good quality of life postoperatively and improvement in the survival rate by preserving pulmonary function, enhancing curability, and increasing the operative indications. These advantages warrant high evaluation of the operation.

Endoscopic ultrasound examination for mediastinal lymph node metastases of lung cancer.

Among patients with primary lung cancer who were admitted to the National Cancer Center Hospital from July 1987 to April 1988 for surgical treatments, 132 underwent preoperative transesophageal endoscopic ultrasound examination (EUS) on mediastinal lymph nodes. Of the 132 patients, 101 were pathologically evaluated and studied in this article. A GF-UM2 radial scanner with 7.5-MHz (Olympus Co Ltd) was used for image examination. The lymph nodes were diagnosed as positive for metastasis when they had thickened images, clear contours, and low echoing images of fusion or lobulation. The results obtained from 509 sites were as follows: sensitivity, 53.6 percent; specificity, 97.5 percent; positive predictive accuracy, 77.1 percent; negative predictive accuracy, 93.1 percent; and overall accuracy, 91.6 percent. The sensitivity rate was 80.6 percent excluding the result of the right superior mediastinal lymph nodes that were difficult to examine for anatomic reasons. Although EUS was considered to be an excellent method in diagnosing lymph node metastases, it had a blind angle in the field. More accurate diagnoses of mediastinal lymph node metastases could be achieved by using EUS and computed tomography (CT) together.