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.

Impact of additional pleurodesis in video-assisted thoracoscopic bullectomy for primary spontaneous pneumothorax.

BACKGROUND: Bullectomy for primary spontaneous pneumothorax has been associated with high postoperative recurrence rates when video-assisted thoracoscopic surgery (VATS) has been used rather than thoracotomy. The aim of this study was to evaluate the efficacy and identify the disadvantages, if any, of adding pleurodesis to VATS bullectomy to prevent recurrent pneumothorax. METHODS: Fifty-three patients who underwent VATS bullectomy with additional pleurodesis for pneumothorax after November 1996 and 50 who underwent VATS bullectomy alone before October 1996 were compared retrospectively in terms of intraoperative factors and postoperative chest pain, pulmonary function, and pneumothorax recurrent rates. Pleurodesis was achieved by electrocauterizing the upper surface of the parietal pleura in a patchy fashion. RESULTS: There were no significant differences between the additional pleurodesis group and the bullectomy alone group in terms of age, sex, operating time, intraoperative bleeding, number of resected bullae, duration of chest drainage, or volume of fluid drained. Postoperative chest pain and pulmonary function were also similar in both groups. A recurrent pneumothorax occurred in one patient (1.9%) in the additional pleurodesis group; this recurrence rate was significantly lower than that for the bullectomy alone group (eight patients, 16%; p = 0.029). Although the mean postoperative follow-up period was considerably shorter in the additional pleurodesis group (38 months [range, 26-49]) than in the bullectomy alone group (63 months [range, 50-72] ), eight (89%) of all nine recurrences occurred within 26 months of surgery-i.e., within the minimum follow-up period for the additional pleurodesis group. CONCLUSIONS: Pleurodesis is a minimally invasive technique that is effective in preventing postoperative recurrences of pneumothorax when added to VATS bullectomy. Additional pleurodesis has no disadvantages vs bullectomy alone in terms of worsening postoperative chest pain or pulmonary function.

Pressure-controlled ventilation via a minitracheostomy tube: experimental study using a mechanical lung model.

To obtain basic data on pressure-controlled ventilation (PCV) via a minitracheostomy tube (MTT), we conducted an experimental study using a mechanical lung model. MTTs with internal diameters of 4.0, 4.5-, and 5.0 mm were used. To examine the effectiveness of PCV via an MTT for the lung with low compliance, the ventilated volumes were measured at compliances ranging from 10 to 50 ml/cmH2O. The alveolar pressures and ventilated volumes of the 4.0-, 4.5-, and 5.0-mm MTTs were about 40%, 50%, and 60% of the values for the 8.0-mm endotracheal tube in the absence of air leakage, respectively, and in the presence of air leakage they fell a further 20%. To obtain a ventilated volume of 500 ml, the inspiratory pressures needed were 40, 30, and 20 cmH2O for the 4.0-, 4.5-, and 5.0-mm MTTs, respectively. In the model of low lung compliance (10 ml/ cmH2O), the ventilated volumes decreased to 40% of those seen in the normal compliance model (50 ml/cmH2O) at each inspiratory pressure, due to greater air leakage. PCV via an MTT produced acceptable ventilated volumes in the lung model with air leakage. However, our results indicate that under conditions of low lung compliance, PCV via a

A case of multiple atypical adenomatous hyperplasia of the lung detected by computed tomography.

Multiple atypical adenomatous hyperplasia (AAH) of both lungs in a 72-year-old male, detected by computed tomography, is reported. The lesions of the right lung were resected for diagnosis via video-assisted thoracoscopic surgery (VATS). The resected specimen had 22 AAH lesions up to 10 mm in size. For nine of these lesions, the expressions of carcinoembryonic antigen (CEA), c-erbB-2 oncoprotein and p53 gene product were examined by immunohistochemistry and the loss of heterozygosity (LOH) on chromosomes was investigated by polymerase chain reaction analysis. These lesions showed a variety of expressions for CEA, c-erbB-2 and p53 oncoprotein. Three of the nine lesions showed LOH on chromosome 13q, although this was not exhibited in the largest one. These results indicate that each AAH in this case has independent genetic abnormalities and is multicentric.

What is the advantage of a thoracoscopic lobectomy over a limited thoracotomy procedure for lung cancer surgery?

BACKGROUND: To clarify any advantages of video-assisted thoracoscopic surgery (VATS) over anterior limited thoracotomy (ALT) for lobectomy in lung cancer, we compared the two procedures in a retrospective analysis. METHODS: Sex- and age-matched (+/- 5 years) lung cancer patients in clinical stage I who underwent lobectomy by means of VATS (n = 33) or ALT (n = 33) were compared in terms of the number of resected lymph nodes, operating time, intraoperative blood loss, duration of postoperative chest tube drainage, and chest pain. Pain was evaluated using a visual analog scale and analgesic requirements. Vital capacity (VC), respiratory muscle strength, and results of a 6-minute walking (6 MW) test were also compared preoperatively and 1 and 2 weeks postoperatively. RESULTS: Compared with the ALT group, the VATS group experienced less pain between postoperative day (POD) 1 and POD 7 (p < 0.05 to 0.001) and had lower analgesic requirements up to POD 7 (p < 0.001). However, there were no significant differences in pain on POD 14. There were also no significant differences in intraoperative factors or in the postoperative impairment of VC, respiratory muscle strength, and 6 MW test results. CONCLUSIONS: Although VATS lobectomy reduces chest pain during the first week after surgery compared with ALT, this advantage is lost within 2 weeks. Both techniques result in similar impairments of pulmonary function, respiratory muscle strength and walking capacity. Therefore, if curative resection of lung cancer by VATS would be technically difficult for any reason, including the surgeon's skill and experience, a limited open thoracotomy would be preferable from the standpoints of safety and the patient's prognosis.

Relationship between existence of lymphatic invasion in peritumoral breast tissue and presence of axillary lymph node metastasis in invasive ductal carcinoma of the breast.

Specimens obtained from 92 patients with invasive ductal carcinoma of the breast by quadrantectomy and axillary lymph node dissection were examined to evaluate the relationship between existence of lymphatic invasion in peritumoral breast tissue and presence of axillary lymph node metastasis. The number of lymphatic invasions was classified into 4 groups (ly0-3) by counting the number of peritumoral lymphatic invasions. In addition, immunohistochemistry for cytokeratin was performed to locate micrometastasis in the dissected lymph nodes. Thirty-seven (40.2%) of 92 cases had foci of lymphatic invasion and 29 (31.5%) cases revealed lymph node metastasis on initial routine examination. The rate of diagnosis of lymph node metastasis assessed by the existence of lymphatic invasion had an accuracy of 84.8%, a sensitivity of 89.7% and a specificity of 82.5%. On the other hand, all 3 cases (4.8%) with micrometastasis detected by immunohistochemistry for cytokeratin, showed lymphatic invasion. The rate of diagnosis after detection of micrometastasis increased and exhibited 88.0% accuracy. In addition, the rate of prediction of lymph node metastasis in cases with tumor larger than 15 mm was also high, and its accuracy was 88.2%. These results suggest that the assessment of peritumoral lymphatic invasion is very useful for predicting the presence of axillary lymph node metastasis including micrometastasis. They also suggest that excision specimens should be examined for lymphatic invasion, and that the results of the examination might be necessary to pick up false-negative cases and those at high risk for lymph node metastasis among patients who have not undergone lymph node dissection based on the result of sentinel lymph node biopsy.

[A case of lung cancer with extensive pleural adhesion, which could be resected by a thoracoscopic middle lobectomy].

A thoracoscopic middle lobectomy was performed for a 78-year-old male with lung cancer associated with extensive pleural adhesion. After peeling off the area of pleural adhesion surrounding the surgical ports by finger, the thoracoscope was inserted into the thorax and then the area of adhesion in the other area was also peeled off under thoracoscope. A pulmonary vein was resected using a stapler. Due to adhesion at the fissures between the lobes, a pulmonary artery and bronchus of the middle lobe were cut from the front of the lung hilum. After that, the fissures between the lobes were also cut using a stapler thus resulting in a complete middle lobectomy. The operation time was 5 hours and 28 minutes, and the intraoperative bleeding was 200 ml. There was no postoperative air leakage, and the chest drain could be removed the day after surgery. In conclusion, even for lung cancer with extensive pleural adhesion, a thoracoscopic lobectomy can still be successfully performed. When a fissure between the lobes is found to adhere, the approach to pulmonary artery and bronchus from the front of the lung hilum is useful for performing a thoracoscopic middle lobectomy.

Early removal of chest drainage tubes and oxygen support after a lobectomy for lung cancer facilitates earlier recovery of the 6-minute walking distance.

The aim of this study was to assess the effects of the early removal of chest tubes and oxygen support lines on the postoperative recovery of patients, who underwent a lobectomy for lung cancer. Forty-two patients, in whom the removal of chest tubes and oxygen support lines was planned for the morning after surgery (subjective group), were matched by sex and age with 42 patients for whom no such action was scheduled (control group). The mean duration of chest tube drainage was 1.5 +/- 0.8 days in the subjective group, which was significantly shorter than the period of 2.8 +/- 1.0 days in the control group (P < 0.001). The mean duration of oxygen support was 1.1 +/- 0.3 days in the subjective group, which was significantly shorter than the period of 3.1 +/- 1.3 days in the control group (P < 0.001). There was no significant difference in the chest drainage volume and oxygen saturation on the morning after surgery between the two groups. We thus compared the postoperative changes in vital capacity (VC) and 6-min walking distance (6MWD) after surgery between the two groups. The early removal of chest tubes and oxygen support lines significantly reduced the impairments of 6MWD 1 week after surgery (P = 0.04) and also diminished the impairments of VC 1 week after surgery but not to a significant extent (P = 0.06). The early removal of chest tubes and oxygen support lines could accelerate the postoperative recovery of 6MWD.

Differentiating early malignant lung tumors from inflammatory nodules to minimize the use of video-assisted thoracoscopic surgery or open biopsy to establish a diagnosis.

To decrease the frequency of video-assisted thoracoscopic surgery (VATS) biopsy being used to diagnose inflammatory nodules, we studied the clinicopathological findings of lung cancers and inflammatory nodules diagnosed by VATS or open-lung biopsy. We studied 46 lung cancers and 47 inflammatory nodules smaller than 30mm in diameter diagnosed by VATS or open-lung biopsy. While the computed tomography (CT) findings were not significantly different between lung cancers and inflammatory nodules, N1 or N2 lung cancers more frequently showed distinct malignant features on CT than T1N0M0 lung cancers (P < 0.05). A review of previous chest X-ray films revealed that those of inflammatory nodules showed new nodules more frequently and nodular enlargement less frequently than those of lung cancer (P < 0.01). Of 13 lung cancers that showed nodular enlargement during a mean 15-month period, 12 were T1N0M0. Nondiagnosable small lung nodules, which had few malignant features on CT and had newly appeared on a chest X-ray film, were more likely to be inflammatory nodules than lung cancers; and even if they were lung cancers, the tumor stage was usually T1N0M0. Thus, to decrease the incidence of VATS biopsy being performed for inflammatory nodules, intensive follow-up by CT until slight nodular enlargement becomes evident could be a means of revealing nondiagnosable small lung nodules without distinct malignant findings, except for nodules found to be enlarging on a review of retrospective films.

Intrathoracic transposition of a pectoralis major and pectoralis minor muscle flap for empyema in patients previously subjected to posterolateral thoracotomy.

The latissimus dorsi muscle flap cannot be used to eliminate an empyema cavity in patients who have previously undergone posterolateral thoracotomy, because of the division of this muscle. Moreover, thoracoplasty alone cannot sufficiently eliminate an empyema cavity that includes the thoracic apex, where space remains between the clavicle and the first rib. Therefore, we constructed a flap from the pectoralis major (P.Ma) and pectoralis minor (P.Mi) muscles to eliminate empyema cavities in five patients who had undergone lobectomy (n = 3) or pneumonectomy (n = 2) via posterolateral thoracotomy from 3 months to 40 years previously. All five patients had bronchopleural fistulae, and because of the previous upper lobectomy or pneumonectomy, they had large empyema cavities including the thoracic apex. Open-drainage thoracotomy was performed due to severe infection, and intrathoracic transposition of the P.Ma and P.Mi muscle flap with simultaneous thoracoplasty was carried out 7-124 weeks (mean 38 weeks) later. The P.Ma and P.Mi muscle flap easily reached the apex space with sufficient obliteration of the empyema cavity. All of the patients remained free of empyema 12-85 months after thoracic closure. The P.Ma and P.Mi muscle flap is useful for eliminating empyema cavities including the thoracic apex in patients who have previously undergone a posterolateral thoracotomy.

Comparison of short-term versus long-term epidural analgesia after limited thoracotomy with special reference to pain score, pulmonary function, and respiratory muscle strength.

To determine the optimal duration of epidural analgesia (EA) after lung cancer surgery, a retrospective analysis was conducted to compare chest pain, pulmonary function, and respiratory muscle strength between patients given EA until postoperative day (POD) 3 and those given EA until POD 8. Each group comprised 25 lung cancer patients who underwent a lobectomy under anterior limited thoracotomy and given continuous thoracic EA using morphine until POD 3 (POD3-EA group) or POD 8 (POD8-EA group). The two groups were matched by sex and age. Postoperative pain from PODs 1 to 12 was evaluated by the pain score and analgesic requirements. The pulmonary function and respiratory muscle strength were measured on POD 7. The POD3-EA group did not experience any increase in pain after withdrawal, but the POD8-EA group did show a significant increase in pain the day after withdrawal (P < 0.05). The pain scores on PODs 8 and 9 in the POD8-EA group were significantly higher than those in the POD3-EA group (P < 0.05). There was no significant difference in pulmonary function and respiratory muscle strength on POD 7 between the two groups. Although the postoperative thoracic EA did not affect pulmonary function and respiratory muscle strength, prolonged thoracic EA after a limited thoracotomy significantly increased the pain after withdrawal, thus negatively affecting postoperative pain control.

[A case of lung and pleural metastases from breast cancer responding to toremifene].

A patient with lung and pleural metastases from breast cancer treated effectively with toremifene is reported. A 62-year-old woman underwent mastectomy for breast cancer, and had high levels of estrogen and progesterone receptor. After 2-years of adjuvant UFT therapy, lung and pleural metastases were seen on a chest x-ray. The patient received a high-dose of toremifene (120 mg/day). After five months with toremifene, a chest x-ray and CT scan showed the disappearance of lung and pleural metastases. No recurrence or metastases have been detected for twenty months to date. No serious side effects were noticed. High-dose toremifene might be an effective therapy for cases of postmenopausal metastatic breast cancer, with high levels of estrogen and progesterone receptor.

Mixing collagen with fibrin glue to strengthen the sealing effect for pulmonary air leakage.

BACKGROUND: To strengthen the sealing effect of fibrin glue for pulmonary air leakage, atelocollagen was mixed with the glue and the mixing effect was examined. METHODS: A mixture of fibrinogen and thrombin with atelocollagen was used as a test sample. The concentrations of atelocollagen were adjusted to levels of 0%, 0.375%, 0.75%, 1.1%, and 1.5%. We next performed air leakage tests on a plastic cap with pin holes and swine lung and also measured the elasticity and the adhesion strength. RESULTS: The pressure required to rupture the sealant on a plastic cap with pin holes increased as the concentration of atelocollagen increased, and the bursting pressures were significantly higher in the glue with 0.75%, 1.1%, and 1.5% of atelocollagen than in the glue without atelocollagen (p < 0.01 and p < 0.001). The air leakage pressure on the swine lung was significantly higher in the glue with 0.375%, 0.75%, and 1.1% of atelocollagen than in the glue without atelocollagen (p < 0.05 and p < 0.01), and it was the highest with 0.75%. The elasticity of the glue significantly increased as the concentration of atelocollagen increased (p < 0.001). However, the adhesion strength of the glue significantly decreased as the concentration of atelocollagen increased (p < 0.05 to p < 0.001). CONCLUSIONS: The mixing of atelocollagen with fibrin glue more effectively sealed pulmonary air leakage due to an increased elasticity of the glue while its adhesion strength decreased. The optimal concentration of atelocollagen in the fibrin glue to obtain the best sealing effect was 0.75%.

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.

Bougienage and balloon dilation using a conventional tracheal tube for tracheobronchial stenosis before stent placement.

In order to achieve urgent restoration of the airways in tracheobronchial stenosis and to make stent placement simpler and safer, we developed a method that allows combined bougienage and balloon dilation via the use of a conventional tracheal tube. Fifteen patients with tracheobronchial stenosis underwent bougienage and balloon dilation using a tracheal tube with a cuff attached, inserted via a tracheostomy, before stent placement. The conventional tracheal tube was inserted via a tracheostomy, the cuff was expanded at the stenotic site, and the tube was fixed to the tracheostomy and left in place for a few days until sufficient dilation was achieved. This procedure was conducted on the trachea in 10 patients, the left main bronchus in three patients, and the right main bronchus in two patients. In all patients, the procedure immediately relieved the obstructive symptoms and dilated the stenosis sufficiently. Thereafter, Dumon stents were inserted in 10 patients, dynamic stents in four patients, and an expandable metallic stent in one patient. The stents were introduced easily with no other dilation procedure after a mean of 5 days from the start of the procedure. For tracheobronchial stenosis, bougienage and balloon dilation using a tracheal tube with an integral cuff via a tracheostomy is a simple and safe method for achieving both urgent relief of airway stenosis and dilation before stent placement.

Granulation stenosis caused by a Dumon stent placed for endobronchial tuberculous stenosis.

Two patients with cicatric tracheobronchial stenosis caused by tuberculosis who suffered granulation stenosis after placement of a Dumon stent are reported. Dumon stents, which were long enough to cover the stenotic sites, were placed in the trachea and left main bronchus of each patient. Granulation tissue grew at both edges of the stent 3 or 4 months after stent placement, which caused restenosis and necessitated removal of the stents. The authors conclude that a Dumon stent for treatment of tracheobronchial stenosis caused by tuberculosis can cause granulation stenosis at the edges of the stent.