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.

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.

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.

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.

Non-serratus-sparing antero-axillary thoracotomy with disconnection of anterior rib cartilage. Improvement in postoperative pulmonary function and pain in comparison to posterolateral thoracotomy.

To examine the usefulness of non-serratus-sparing antero-axillary thoracotomy (AAT) with disconnection of anterior rib cartilage for curative resection of lung cancer, we used retrospective analysis to compare mortality, morbidity, hospital stay, time for thoracic opening, postoperative pulmonary function, and chest pain between AAT and posterolateral thoracotomy (PLT). Subjects were 50 lung cancer patients who underwent lobectomy via AAT (n = 25) or PLT (n = 25), who were matched by sex and age. Chest pain was evaluated using a visual analog scale, a McGill pain questionnaire, and analgesic requirements up to 6 months after surgery. AAT offered adequate exposure for lobectomy and mediastinal lymph node dissection. No difference was observed between the AAT and PLT groups in postoperative mortality, morbidity, or hospital stay. Times for thoracic opening were significantly shorter in AAT than in PLT (p < 0.001). FEV1 and vital capacity 1 week after surgery were significantly preserved in patients with AAT compared with patients with PLT (p < 0.05). Chest pain was significantly reduced in AAT patients compared with PLT patients on 1 day and from 14 days to 6 months after surgery (p < 0.01 to p < 0.001). We conclude that AAT is a reasonable thoracotomy alternative to standard PLT for curative lung cancer resection, because of its adequate exposure, shortened opening time, diminished impairment of postoperative pulmonary function, and reduced chronic postoperative pain.

Clara cell protein correlation with hyperlipidemia.

Serum levels of protein 1 (P1), a Clara cell secretory protein, in 746 healthy subjects were measured and their correlations with different types of serum lipids and lipoproteins-that is, triglyceride (TG), total cholesterol (TCh), free cholesterol (FCh), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and apoproteins (apo) A-I, A-II, and B-were examined. P1 serum levels were examined for their correlation with body mass index (BMI), and were compared for 47 obese, 70 normal, and 17 lean males. P1 serum levels in 69 patients with diabetes mellitus and 24 patients with atherosclerotic stenosis of the carotid artery or coronary artery were also compared to those in healthy control subjects. P1 showed a significant positive correlation with TG, TCh, FCh, apo A-I, apo A-II, apo B, and BMI (r = 0.93, 0.26, 0.42, 0.11, 0.35, 0.58, and 0.20, respectively; p < 0.0001 to 0.05), and an inverse correlation with HDL (r = -0.32; p < 0.01). P1 values in obese men (mean +/- SD: 139.2 +/- 98.2 micrograms/L) were significantly higher than those in normal (90.3 +/- 57.1) and lean ones (65.6 +/- 40.8) (p < 0.01). In both diabetic and atherosclerotic patients, P1 serum levels did not significantly differ from those in healthy subjects. From these results, we conclude the following: (1) the serum levels of P1 correlate significantly with those of lipids and lipoproteins; (2) P1 serum levels increase in the case of obesity.

Opening of infectious giant bulla with use of video-assisted thoracoscopic surgery.

In 5 cases, an infectious giant bulla was opened with the use of video-assisted thoracoscopic surgery (VATS). Because all bullae adhered to the thoracic wall and were noncommunicating with the airway, they were opened without complete resection, leaving their inside walls at the lung and lateral walls on the thoracic wall. The expansion of remnant lung was excellent, and postoperative air leakage did not occur in any case. The postoperative vital capacity and FEV1 improved significantly over the preoperative condition (p<0.01). Because the bronchial communication of bulla is frequently obliterated after infection within the bulla, opening of a bulla is curative and simpler, more effective, and less invasive than complete resection.

Lung adenocarcinomas diagnosed by open lung or thoracoscopic vs bronchoscopic biopsy.

STUDY OBJECTIVES: To examine the characteristics of peripheral lung adenocarcinomas diagnosed by open lung or video-assisted thoracoscopic surgery (VATS) biopsy. DESIGN: We used retrospective analysis to compare tumor stage, pleural involvement, central tumor fibrosis, and the number of bronchi or vessels involved with tumors of small peripheral lung adenocarcinomas diagnosed by bronchoscopic biopsy. PATIENTS: Subjects had lung adenocarcinomas diagnosed by open lung or VATS (n=22) and those diagnosed by bronchoscopic biopsy (n=22), which were matched by tumor size. RESULTS: The T1N0M0 tumor was notably more frequent in the open lung or VATS group (77.3%) than in the bronchoscopic biopsy group (36.4%) (p<0.01). Tumors invading beyond the pleural surface were less frequent in the open lung or VATS group (4.5%) than in the bronchoscopic biopsy group (40.9%) (p<0.01). The grade of in-tumor central fibrosis--a malignancy factor and the cause of bronchi or vessel involvement with tumors-was significantly lower in the open lung or VATS group than in the bronchoscopic biopsy group (p<0.01). The number of bronchi or vessels involved with tumors was significantly fewer in the open lung or VATS group than in the bronchoscopic biopsy group (p<0.001). CONCLUSIONS: (1) Lung adenocarcinomas diagnosed by open lung or VATS biopsy were more frequently T1N0M0 than those diagnosed by bronchoscopic biopsy, which was caused by low grade of central tumor fibrosis rather than small tumor size. (2) They were infrequently diagnosed by bronchoscopic biopsy because few bronchi were involved by tumors due to the low grade of central tumor fibrosis. (3) Small pulmonary nodules not diagnosable by bronchoscopic biopsy should be diagnosed aggressively using VATS biopsy to detect early-stage lung cancer.

Gelatin-resorcinol-formaldehyde-glutaraldehyde glue-spread stapler prevents air leakage from the lung.

BACKGROUND: To reinforce the staple line of the emphysematous lung and thereby prevent air leakage during thoracoscopic operations, we have developed a procedure of lung excision that uses a gelatin-resorcinol-formaldehyde-glutaraldehyde (GRFG) glue-spread stapler. METHODS: Formaldehyde-glutaraldehyde (FG) jelly is prepared by mixing FG fluid with 2.5% sodium carboxymethyl cellulose. The FG jelly is placed in the stapler groove and staple holes, and a gelatin-resorcinol (GR) mixture is applied. The GRFG glue-spread stapler was applied to emphysematous lung cutting during thoracoscopic operations in 10 cases. RESULTS: An adhesion-strength test showed no difference in glue adhesion between FG fluid and FG jelly. An experiment using swine lung showed that with this newly developed stapler, no resistance in firing occurred, and GRFG glue covered every staple hole. Clinical application in 10 cases with emphysematous lung demonstrated no air leakage from the staple line, even long after the operation. CONCLUSIONS: Emphysematous lung excision using the GRFG glue-spread stapler during thoracoscopic operations is useful in preventing air leakage from the staple line and is a simple, safe, and low-cost procedure.

Colored collagen is a long-lasting point marker for small pulmonary nodules in thoracoscopic operations.

BACKGROUND: To locate small deep pulmonary nodules under thoracoscopy, we developed a long-lasting point marker termed "colored collagen." METHODS: Colored collagen is composed of 0.8% atelocollagen, 5% methylene blue, and 32% contrast medium. The affinity between atelocollagen and methylene blue was examined in a washing test using 2 mol/L of NaCl. For clinical application, a computed tomography-guided colored collagen injection was performed in 11 patients to localize 11 deep pulmonary nodules, which were less than 20 mm in diameter. RESULTS: The washing test showed that atelocollagen and methylene blue combined with each other firmly. An experimental study using rabbit lung showed that the colored collagen stayed at the injected site for 10 days without toxicity. In clinical application, the colored collagen could be seen as a clear spot using the thoracoscopy 1 to 4 days after the injection in all of the 11 pulmonary nodules. There was no complication except for a slight pneumothorax in 2 patients. CONCLUSIONS: The colored collagen, because it stays in the injected site for a long time, solves the problem of the single dye injection method, which requires both a computed tomographic scan and an operating room simultaneously, and also the colored collagen, because of its point dyeing, can mark the nodule more accurately than a single dye.

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%.

Synchronous reconstruction of the trachea and innominate artery in thyroid carcinoma.

A 50-year-old woman underwent combined resection and reconstruction of the trachea and the innominate artery synchronously for thyroid carcinoma. The pedicled thymus was interposed between the anastomosis of the trachea and the artery. The postoperative course was satisfactory. Synchronous reconstruction of the artery and trachea may thus prove to be safe, and interposition of the thymus flap may be useful in the prevention of secondary graft infection from the tracheal anastomosis.

Daily and long-term balloon dilation via minitracheostomy in cicatric bronchial stenosis.

We developed balloon dilation for bronchial stenosis via minitracheostomy. The balloon catheter was introduced via minitracheostomy into the stenotic bronchus. The balloon was inflated 4 hours per day. We conducted this procedure for a tuberculous cicatric stenosis of the left lower lobe bronchus. The bronchus was sufficiently dilated after eight applications. Compared with conventional balloon dilation via the mouth, the patient had less discomfort and could undergo treatment for a longer time and more frequently.

Double stenting for esophageal and tracheobronchial stenoses.

BACKGROUND: We examined the complications and outcomes of placing stents for both esophageal and tracheobronchial stenoses. METHODS: We placed stents for both esophageal and tracheobronchial stenoses in 8 patients (7 with esophageal cancer and 1 with lung cancer). Covered or noncovered metallic stents were used for the esophageal stenoses, except in 1 patient treated with a silicone stent. Silicone stents were used for the tracheobronchial stenoses. The grades of esophageal and tracheobronchial stenoses were scored. RESULTS: All patients experienced improvement of grades of both dysphagia and respiratory symptoms after stent therapy. The complications were: (1) 2 patients suffered respiratory distress after placement of the esophageal stent because of compression of the trachea by the stent; and (2) 3 patients developed new esophago-tracheobronchial fistulae, and 2 patients had recurring fistula symptoms because of growth of preexisting fistulae after the stent placement, which were caused by pressure from the 2 stents. Despite the fistulae, the 5 patients treated with covered metallic stents did not complain of fistula symptoms, but 2 patients treated with noncovered metallic or silicone stents did complain. CONCLUSIONS: For patients with both esophageal and tracheobronchial stenoses, a stent should be introduced into the tracheobronchus first. Because placement of stents in both the esophagus and tracheobronchus has a high risk of enlargement of the fistula, a covered metallic stent is preferable for esophageal cancer involving the tracheobronchus.

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.