A randomized, open-label, phase III trial comparing amrubicin versus docetaxel in patients with previously treated non-small-cell lung cancer.

Background: Amrubicin is approved for treating non-small-cell lung cancer (NSCLC) and small-cell lung cancer. However, no direct comparisons between amrubicin and docetaxel, a standard treatment for NSCLC, have been reported. Patients and methods: We conducted a randomized phase III trial of Japanese NSCLC patients after one or two chemotherapy regimens. Patients were randomized to amrubicin (35 mg/m2 on days 1-3 every 3 weeks) or docetaxel (60 mg/m2 on day 1 every 3 weeks). Outcomes included progression-free survival, overall survival, tumor responses, and safety. Results: Between October 2010 and June 2012, 202 patients were enrolled across 32 institutions. Median progression-free survival (3.6 versus 3.0 months; P = 0.54) and overall survival (14.6 versus 13.5 months; P = 0.86) were comparable in the amrubicin and docetaxel groups, respectively. The overall response rate was 14.4% (14/97) and 19.6% (19/97) in the amrubicin and docetaxel groups, respectively (P = 0.45). The disease control rate was 55.7% in both groups. Adverse events occurred in all patients, and included grade ≥3 neutropenia occurred in 82.7% and 78.8% of patients in the amrubicin and docetaxel groups, respectively, grade ≥3 leukopenia occurred in 63.3% and 70.7%, and grade ≥3 febrile neutropenia occurred in 13.3% and 18.2% of patients in the amrubicin and docetaxel groups, respectively. Of eight cardiac-related events in the amrubicin group, three were considered related to amrubicin and resolved without treatment discontinuation. Conclusions: This was the first phase III study to compare amrubicin and docetaxel in patients with pretreated NSCLC. Amrubicin did not significantly improve the primary endpoint of PFS compared with docetaxel. Clinical trial registration: NCT01207011 (ClinicalTrials.gov).

[Mediastinal germ cell tumor with somatic-type malignancy successfully treated with chemotherapy followed by surgical resection combined with lobectomy: report of a case].

A 28-year-old male visited our hospital with complaint of chest pain. Clinical examination revealed a huge mediastinal mass which was diagnosed as non-seminomatous germ cell tumor. The patient underwent 5 cycles of chemotherapy (bleomycin, etoposide, and cisplatin) followed by resection of the tumor combined with left upper lobectomy. Final pathological diagnosis was germ cell tumor with somatic-type malignancy. While the prognosis of mediastinal germ cell tumor with somatic-type malignancy is known to be extremely poor, multimodality at an early stage is the key to successful treatment.

[Right pneumonectomy for typical bronchial carcinoid in a 19-year-old man].

A 19-year-old man visited our hospital with a diagnosis of carcinoid arising from the right intermediate bronchus. Clinical examination revealed T3N1M0 lung cancer, so right pneumonectomy with mediastinal lymph node dissection was performed after obtaining informed consent from the patient and his parents. Final pathological diagnosis was T2N2M0 typical carcinoid. Typical bronchial carcinoid with lymph node metastasis is very rare in patients under 20 years old.

[Bleeding by staple in video-assisted thoracoscopic interlobar plasty of the lung].

A 58-year-old man underwent video-assisted thoracoscopic right upper lobectomy. He was discharged without event on postoperative day 8. On postoperative day 12, he visited emergently in a pre-shock state. Chest radiography showed massive right pleural effusion and intrathoracic bleeding was suspected. Thoracotomy was immediately performed and the bleeding point was identified as an internal thoracic artery. Hemostasis was performed but no cause of arterial injury was apparent. In another case, we had seen incidental snag the pleura on the internal thoracic artery by a staple from interlobar plasty of the lung. We therefore suspected that the cause in this case was injury of the internal thoracic artery by staple during video-assisted thoracoscopic interlobar plasty of the lung.

[Lobectomy for local recurrence of lung cancer after 3-dimensional-conformal radiotherapy].

An 85-year-old man was diagnosed as having primary cancer located in the middle lobe (squamous cell carcinoma cT1N0M0 stage IA). Because of his general conditions and status as an octogenarian, 3-dimensional-conformal radiotherapy (3D-CRT, 75Gy in 25 fractions) was selected. The therapeutic response was partial remission, and the adverse reaction was radiation pneumonitis (grade 2). Seventeen months after 3D-CRT, local recurrence was detected. Surgery was performed. Thoracoscopic findings demonstrated scarring fibrosis in the middle lobe and there was no adhesion in the pulmonary hilum. Therefore, video-assisted thoracoscopic lobectomy was performed safely. The patient was discharged on the 10th days post operatively without complication. After 12 months follow-up, there has been no recurrence.

[Thymic carcinoid accompanied by elevation of serum gastrin-releasing peptide precursor; report of a case].

A 74-year-old male was admitted with an abnormal mediastinal shadow. Computed tomography (CT) and magnetic resonance imaging (MRI) of the thorax showed an anterior mediastinal mass without invasion to the ascending aorta and pulmonary artery. In addition, serum gastrin-releasing peptide precursor (Pro GRP) was increased (60.6 pg/ml, normal range <46 pg/ml). Video-assisted thoracoscopic biopsy demonstrated that the mass was thymic carcinoid. Therefore, median sternotomy was performed to facilitate thymectomy, including the tumor with partial resection of the left upper lobe and pericardium. The patient received mediastinal irradiation postoperatively. The postoperative serum level of Pro GRP decreased to the normal limit 6 months later. Although a biological relationship between Pro GRP and thymic carcinoid was not proven, it might be useful marker for detecting tumor recurrence.

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.

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.

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

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.

[Dumon stent placement via endotracheal tube].

We conducted a Dumon stent placement via endotracheal tube for 10 patients with airway stenosis. The conventional endotracheal tube is inserted beyond the stenosis site; this procedure is conducted with the use of a flexible bronchoscope under general anesthesia. The Dumon stent is folded and inserted into the endotracheal tube and is then introduced into the stenosis site with the use of a cylindrical-tipped stainless steel wire as a pusher. Although the Dumon stents were placed using a rigid bronchoscope for the first 7 patients, the present procedure was used for the latest 10 patients. Compared with the rigid bronchoscope technique, this procedure is suitable for the placement of a larger stent for a shorter time. It has the following advantages over the rigid bronchoscope technique: (1) the use of an endotracheal tube and flexible bronchoscope makes the stent placement easier for the practitioner and less stressful for the patient; (2) because of the flexibility of the endotracheal tube, a Dumon stent can be placed easily, even in the left main bronchus or in a markedly shifted trachea or bronchus, and also in a patient who has difficulty in expanding the neck; (3) a stent can be placed safely in a patient with severe tracheal stenosis and orthopnea. The present procedure does, however, have the disadvantage that it is difficult to control the direction of the tip of the endotracheal tube. We concluded that the present procedure could be a useful method for Dumon stent placement.

Maitake (Grifola frondosa) improve glucose tolerance of experimental diabetic rats.

We have previously reported that rats with diabetes induced by injecting streptozotocin into neonates showed remarkably lower blood glucose, urine volume, and glucosuria after administration of Maitake (Grifola frondosa). In the present study, we investigated the effects of Maitake on insulin concentration, organ weight, serum composition, and islets of Langerhans in streptozotocin-induced diabetic rats using the same method. The diabetic rats were produced by injecting 80 mg/kg B.W. streptozotocin into 2-d-old neonates. From the age of 9 wk, the rats were given experimental diets for 100 d. The diabetes and control groups were given either diets containing 20% Maitake (DM and CM groups) or control diets (D and C groups). During administration of the experimental diets, we measured body weight, food intake, amount of feces, and serum insulin concentration at glucose loading. The glucose tolerance test was performed at the 10th week after the start of the experimental diets. The D group had an initial fasting blood glucose of 225+/-49 mg/dL, and a maximum blood glucose of 419+/-55 mg/dL at 60 min. In the DM group, however, the initial fasting blood glucose was 170+/-23 mg/dL, and the maximum blood glucose was 250+/-41 mg/dL at 15 min. Both values were markedly lower than those in the D group (p<0.05). The insulin concentration at 15 min. after glucose loading in the DM group was 41+/-16 microU/mL, which was significantly higher than that in the D group (15+/-7 microU/mL) (p<0.05). After the 100-d experimental period, blood samples were collected. The fructosamine level was significantly lower in the DM group (152+/-21 mmol/L) than in the D group (185+/-13 mmol/L). The concentration of 1.5-A.G. (1.5-anhydro glucitol) was significantly higher in the DM group (9.33+/-2.42 microg/mL) than in the D group (1.33+/-0.52 microg/mL). Observation of insulin antibody stain in the Langerhans cells of the pancreas using ABC method showed a decrease insulin antibody stain in the D group. The cells of the DM group were stained more darkly than those of the D group. From these results, we postulated that the bioactive substances present in Maitake can ameliorate the symptoms of diabetes.

[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.

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.

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.

[A case of post-thymomectomy myasthenia gravis after extrapleural pneumonectomy for invasive thymoma which necessistated long-term mechanical ventilation].

The patient was a 58-year-old male with invasive thymoma which had disseminated in the left thorax and was histologically a polygonal cell type lesion. While the serum value of anti-acetylcholine receptor antibody was high before surgery, there were signs of myasthenia gravis. After preoperative chemotherapy, a thymectomy and left panpleuropneumonectomy were conducted. Forty days after surgery, the patients suffered post-thymomectomy myasthenia gravis, which necessitated mechanical ventilation for 6 months. Despite steroid therapy and 17 plasmapheresis procedures the tidal volume increased by little more than 200-250 ml during that time. The causes of ventilatory failure, therefore, were probably decreased pulmonary function due to extrapleural pneumonectomy and the myasthenia gravis. According to the literature, polygonal cell type thymomas with high serum levels of anti-acethycholine receptor antibody have higher incidences of post-thymomectomy myasthenia gragvis than other ones. Therefore, the risk of post-thymomectomy myasthenia gravis should be kept in mind when extrapleural pneumonectomy for invasive thymoma is being considered, especially in the cases of this type.

[Low body mass index and exercise capacity in patients with chronic obstructive pulmonary disease (COPD)].

This study examined retrospectively the relationships between body weight and exercise capacity in patients with chronic obstructive pulmonary disease (COPD). Seventeen patients with a %FEV1 less than 55% (mean +/- SD 36% +/- 8.8%) and minimum body weights of the body mass index (BMI) less than 20 (17.3 +/- 1.7) performed incremental exercise testing using a treadmill. Seventeen %FEV1-matched control patients with normal body weights were selected. There were no significant differences in the patients' characteristics or their pulmonary function tests (including vital capacity, carbon monoxide diffusing capacity, and arterial blood gases). Low BMI patients Is this the weaning of (67.8 +/- 6.3 years old) were younger than the control patients (73.1 +/- 8.5 years old), but the difference was not statistically significant. The exercise capacities of low BMI patients were significantly superior to those of the control patients (316.5 +/- 171.5 seconds vs 204.1 +/- 116.3 seconds, p = 0.038) and total walking distance without statistical significance (194.9 +/- 117.0 m vs 125.7 +/- 98.0 m, p = 0.071). Also, low BMI patients achieved higher maximal minute ventilation volume during exercise than the controls. The major factor limiting exercise in patients with low BMI was ventilation. Moderately low body weight may not be a risk factor in Japanese COPD patients.