[Thoracoscopic surgery for intractable pneumothorax under epidural and local aesthesia].

Thoracoscopic surgery under epidural and local anesthesia for intractable pneumothorax were performed in 26 patients. A total of 29 thoracoscopic operation were performed in 26 patients. Twenty-three patients undervent only a single thoracoscopic operation, and 3 patients underwent twice thoracoscopic operations. We could control the air leak of intractable pneumothorax with the covering of polyglycolic acid sheets using aerosolized fibrin glue in 25 patients. In all patients postoperative course was uneventful and there was no operative death.

[Successful removal of an intrapulmonary aberrant needle under video-assisted thoracoscopic surgery; report of a case].

Intrapulmonary aberrant needles are rare in clinical practice. We report the successful removal of intrapulmonary aberrant needle. A 59-year-old man, though he was asymptomatic, was referred to our department after an abnormal shadow had been detected on a chest X-ray. Chest X-ray and chest computed tomography (CT) showed a foreign body suspected to be a metal artifact in the left upper lobe. It was diagnosed as an intrapulmonary aberrant needle and an operation under video-assisted thoracoscopic surgery was performed. Using perioperative fluoroscopy, we could confirm the location of the needle and remove it successfully. An intrapulmonary aberrant needle should be removed surgically, even if the patient is asymptomatic, due to the development of lung abscess or pyothorax and the risk containing harmful matter to health.

Preoperative induction chemotherapy with cisplatin and irinotecan for pathological N(2) non-small cell lung cancer.

We conducted a phase I/II study to investigate whether the surgical resection after induction chemotherapy with cisplatin and irinotecan was feasible and could improve the treatment outcome for patients with pathological N(2) non-small cell lung cancer. Fifteen patients with stage IIIA non-small cell lung cancer having mediastinal lymph node metastases proved by mediastinoscopy were eligible. Both cisplatin (60 mg m(-2)) and irinotecan (50 mg m(-2)) were given on days 1 and 8. Patients received two cycles of chemotherapy after 3-4 weeks interval. Induction was followed by surgical resection in 4-6 weeks. Patients who had documented tumour regression after preoperative chemotherapy received two additional cycles of chemotherapy and other patients received radiotherapy postoperatively. After the induction chemotherapy, the objective response rate was 73%. All the 15 patients received surgical resection and complete resection was achieved in 11 (73%) patients. There was no operation-related death and one death due to radiation pneumonitis during postoperative radiotherapy. The median time from entry to final analysis was 46.5 months, ranging from 22 to 68 months. The 5-year survival rate was 40% for all the 15 patients and it was 55% for the 11 patients who underwent complete resection. We conclude that the surgical resection after induction chemotherapy with cisplatin and irinotecan is feasible, and associated with low morbidity and high respectability.

Pulmonary function, postoperative pain, and serum cytokine level after lobectomy: a comparison of VATS and conventional procedure.

BACKGROUND: Although lobectomy by the video-assisted thoracic surgical (VATS) approach is assumed to be less invasive than lobectomy by the standard posterolateral thoracotomy (PLT) approach, it has not been scientifically proven. METHODS: Twenty-two consecutive, nonrandomized patients, underwent either a VATS approach (n = 13) or a posterolateral thoracotomy approach (n = 9) to perform pulmonary lobectomy for peripheral lung cancers in clinical stage I. Pain and serum cytokines were measured until postoperative day (POD) 14. Pulmonary function tests were performed on POD 7 and POD 14. RESULTS: Postoperative pain was significantly less in the VATS group on PODs 0, 1, 7, and 14. Recovery of pulmonary function was statistically better in the VATS group. Negative correlations between the recovery rates of pulmonary function and postoperative pain were observed on POD 7. The serum interleukin-6 level in the PLT group was significantly elevated on POD 0 compared with the VATS group (posterolateral thoracotomy: 21.6+/-24.3 pg/mL; VATS: 4.1+/-7.9 pg/mL, p = 0.03). CONCLUSIONS: Lobectomy by the VATS approach generates less pain and cytokine production, and preserves better pulmonary function in the early postoperative phase.

Reduced expression of REIC/Dkk-3 gene in non-small cell lung cancer.

Dickkopfs (Dkks) are secretory glycoproteins and are important for inducing amphibian head formation. Some Dkks have the ability to antagonize the Wnt proto-oncoprotein, which can promote cell proliferation and transformation when it is mutated or overexpressed. We recently cloned the REIC/Dkk-3 gene, one of the Dkks, and found that expression of the gene was markedly decreased in many human immortalized and tumor-derived cell lines. To further investigate the function of the REIC/Dkk-3 gene in vivo, the gene expression was quantified in 57 surgically-resected non-small cell lung cancer (NSCLC) tissues and their adjacent normal lung tissues by real-time quantitative PCR analysis based on TaqMan methodology. The REIC/Dkk-3 mRNA level was significantly lower in NSCLC tissues than in normal lung tissues. Reduced expression of REIC/Dkk-3 in NSCLC was observed in 36 (63%) of the 57 tumors. Reduced expression of REIC/Dkk-3 was frequently observed in poorly differentiated adenocarcinoma and squamous cell carcinoma. These results indicate that reduced expression of REIC/Dkk-3 may be correlated with rapid cell proliferation in human NSCLC.

Living-donor lobar lung transplantation for primary ciliary dyskinesia.

A ventilator-dependent patient with primary ciliary dyskinesia underwent successful living-donor lobar lung transplantation. The case was a 24-year-old woman who had developed recurrent lower respiratory infection and became ventilator-dependent due to severe bronchiectasis. Transmission electron microscopy of the resected bronchus demonstrated inner dynein arm deficiency.

Microsatellite instability correlates with normal expression of cyclin E in hepatocellular carcinomas.

It has been reported that microsatellite instability (MSI) strongly correlates with carcinogenesis and cancer progression. In the present study, we studied the incidence of MSI at 5 polymorphic microsatellite markers (D5S406, D13S153, D16S402, D17S796, and poly(A) tract BAT26), the expression of G1 cyclins (cyclin A, cyclin D and cyclin E), and Ki-67 labeling index in 30 surgically resected hepatocellular carcinomas (HCCs) and their adjacent non-cancerous tissues. The results of analysis showed that 43% of HCCs exhibited MSI in one locus, 10% in two loci, and 3% in three loci. Overexpressions of cyclin E and cyclin A were observed in 57% and 83% of HCCs, respectively. MSI in HCCs, however, correlated with normal expressions of cyclin E and cyclin A and with a low labeling index of Ki-67. Thus, patients with HCCs exhibiting MSI at these 5 markers may have less involvement of G1/S disregulation and may have better prognosis than other patients with HCC.

Intrapulmonary lymph nodes enlarged after lobectomy for lung cancer.

A 62-year-old man, who had had a left upper lobectomy for mucoepidermoid lung carcinoma, was admitted again 3 months later because of enlargement of four small nodules in the left lower lobe. A computed tomography-guided needle aspiration biopsy obtained insufficient material for diagnosis, and because pulmonary metastases were suspected, two of the four tumors were extirpated. Intraoperative frozen section found the nodules to be intrapulmonary lymph nodes. Intrapulmonary lymph nodes should be included in the differential diagnosis of coin lesions in the peripheral lung field.

Short-term inhaled nitric oxide in canine lung transplantation from non-heart-beating donor.

BACKGROUND: Use of lungs harvested from non-heart-beating donors (NHBDs) would increase the pulmonary donor pool; however, this strategy would have higher risk of early postoperative graft dysfunction due to unavoidable warm ischemic time. We evaluated the effects of short-term inhaled nitric oxide (NO) during reperfusion in canine left single-lung allotransplantation from a non-heart-beating donor. METHODS: The donor dogs were sacrificed without heparinization and left at room temperature for 3 hours. Then, recipient dogs received a left single-lung allotransplantation. After implantation, the right bronchus and pulmonary artery were ligated. In group 1 (n = 6), NO gas was administered continuously at a concentration of 40 parts per million throughout a 6-hour assessment period. In group 2 (n = 6), NO gas was administered for the initial 1 hour during reperfusion. In group 3 (n = 6), nitrogen gas was administered for control. RESULTS: Groups treated with NO exhibited lower pulmonary vascular resistance, as well as improved survival and oxygenation. There was no significant difference in these parameters between group 1 and group 2. Myeloperoxidase activity was significantly lower in NO-treated groups. CONCLUSIONS: Inhaled NO during reperfusion is beneficial in lung transplantation from non-heart beating donors. The beneficial effect is obtained mainly during the first hour of reperfusion.

Telomerase activity and Bcl-2 expression in non-small cell lung cancer.

Bcl-2 and p53 are the most relevant proteins in apoptosis and tumor development. Telomerase functions in the maintenance of telomeres and is indispensable for immortalization. Bcl-2 was reported as a direct modulator of telomerase activity, and a correlation between p53 and telomerase activity was reported. The aim of this study was to determine the relationships between Bcl-2, p53, and telomerase activity in non-small cell lung cancer. Immunostaining for Bcl-2, p53, and Ki-67 was performed in 64 surgically resected non-small cell lung cancers, and a fluorescence-based telomeric repeat amplification protocol assay for semiquantitative analysis of telomerase activity was done. Twenty-eight (44%) and 33 (52%) cases showed positive staining for Bcl-2 and p53, respectively. Bcl-2 expression was associated with negative lymph node involvement (P = 0.0248). p53 expression was associated with tumor size (P = 0.0244), p stage (P = 0.0391), and proliferative activity (P = 0.0004). Telomerase activity was detected in 89.1% and was closely associated with aggressive clinicopathological features. Telomerase activity was higher in p53-positive tumors (P < 0.0001), but represented no correlation with Bcl-2 expression (P = 0.3239). Interestingly, when the cases were stratified by histological grade and the level of Ki-67 labeling index, Bcl-2 expression was more clearly associated with favorable clinicopathological features and lower telomerase activity only in low-grade tumors. In conclusion, p53 is closely associated with telomerase activity. In low-grade tumors, Bcl-2 is inversely correlated to telomerase activity. Our results suggest that the biological role of the Bcl-2 protein alters according to tumor aggressiveness, thereby cofunctioning with telomerase against genetic instability.

Prognostic value of vascular endothelial growth factor expression in primary lung carcinoma.

To investigate whether an association exists between vascular endothelial growth factor (VEGF) expression and tumor prognosis in primary lung carcinoma, we used immunohistochemical techniques to analyze microvessel density and VEGF expression in lung carcinoma tissue from 98 patients. Tissue had been fresh-frozen at the time of operation and preserved for more than 5 years. The results indicated that VEGF expression was positive for 50 of the 98 patients (51.0%), with 27 (27.6%) being weakly positive and 23 (23.5%) being strongly positive. The microvessel density in tissue showing weakly positive and strongly positive VEGF expression was significantly higher than that in VEGF-negative tumor tissue (P < 0.05: negative vs. weakly positive, P < 0.01: negative vs. strongly positive), we showed demonstrating that VEGF expression was significantly associated with intratumoral microvessel density. The 5-year survival rates were 8.7% for strongly VEGF-positive patients, 43.9% for weakly VEGF-positive patients and 79.2% for VEGF-negative patients, respectively (P < 0.01: negative vs. weakly positive or strongly positive). Furthermore, multivariate analysis employing multiple regression analysis indicated that VEGF expression correlates highly with the overall survival rates of patients with primary lung carcinoma. Two variables, N status and VEGF expression, were found to be significant prognostic factors (P < 0.01). The results of this study suggest that VEGF expression is associated with intratumoral microvessel density. VEGF expression may constitute important independent prognostic evidence that can help us in predicting the outcomes of patients with primary lung carcinomas.

Referrals for lung transplantation in Japan. Unique indications and necessity of living-donor lobar lung transplantation.

OBJECTIVES: The purpose of this study was to review all referrals to our lung transplant program and to find realistic options for accepted candidates in Japan. METHODS: During the period from April 1992 to August 1999, 45 referrals were received. After screening, 22 of the referred patients were admitted for an extensive inpatient evaluation, and 15 of these were accepted as candidates for transplantation. RESULTS: The indication was primary pulmonary hypertension in 9, bronchiectasis in 2, lymphangioleiomyomatosis in 2, idiopathic pulmonary fibrosis in 1, and pneumoconiosis in the other 1. Two of those with primary pulmonary hypertension went to the USA and there received bilateral lung transplant. One with bronchiectasis received living-donor lobar lung transplantation in our center. These three recipients are alive and doing well during the follow-up period of 11 to 69 months. Among the 12 patients who have not received lung transplant, 5 patients have died while waiting. CONCLUSIONS: Indications for lung transplant are quite distinct in Japan, and primary pulmonary hypertension is the most frequent indication. Living-donor lobar lung transplantation is a realistic option for properly selected candidates.

Predictors of improvement in FEV1 (forced expiratory volume in 1s) after lung volume reduction surgery.

We evaluated various preoperative and operative factors to identify the predictors of improvement in forced expiratory volume in 1s (FEV1) after lung volume reduction surgery (LVRS). Fifty-eight emphysema patients received bilateral LVRS either via a sternotomy (n = 53) or by thoracoscopy (n = 5). The patients were divided into the following two groups: group I (n = 17), patients whose FEV1 improved by less than 20%; group II (n = 41), patients whose FEV1 improved by more than or equal to 20%. The preoperative factors (age, degree of dyspnea, oxygen use, steroid use, pulmonary function test, arterial blood gas, pulmonary hemodynamics, 6-min walking distance) and operative factors (removed lung weight, number of staplers) were both similar between the two groups. Upper lobe type emphysema was more frequently seen in group II and the average improvement in FEV1 was significantly better in the patients with upper lobe type emphysema (62.8% +/- 8.5%) than lower lobe type (36.9% +/- 7.6%) and mixed type (35.5% +/- 6.5%), P < 0.01. Severe pleural adhesion was more frequently found in group I and the average improvement in FEV1 was also significantly lower in patients with severe pleural adhesion (19.8% +/- 6.4%) than mild-to-moderate adhesion (46.8% +/- 5.3%) and no-to-minimal adhesion (62.3% +/- 10.4%), P < 0.01. These results lead us to conclude that upper lobe type emphysema may thus be a predictor of better FEV1 improvement while severe pleural adhesion is considered to be a predictor of a poorer FEV1 improvement after bilateral LVRS.

Effects of inhaled nitric oxide in a canine living-donor lobar lung transplant model.

OBJECTIVE: In living-donor lobar lung transplantation, early severe graft dysfunction can occur if the size or amount of transplanted lung tissue is insufficient. The purpose of this study was to evaluate the effects of inhaled nitric oxide on early pulmonary function in a canine bilateral living-donor lobar lung transplant model. METHODS: Sixteen pairs of mongrel dogs with a donor/recipient weight ratio less than 1.2 were used. The donor lung bloc was extirpated after heparinization. Right middle, lower and cardiac lobes were implanted as a right lung of the recipient and left lower lobe was implanted as a left lung without cardiopulmonary bypass. In Group 1 (n = 9), nitric oxide gas was administered continuously at a concentration of 40 parts per million prior to reperfusion of the right lung throughout the 6-hour assessment period after transplantation. In Group 2 (n = 7), nitrogen gas was administered in the same manner as nitric oxide, for control. RESULTS: At the end of assessment, the survival rate was 89% (8/9) in Group 1 and 57% (4/7) in Group 2. The arterial oxygen tension in Group 1 was significantly higher than that in Group 2. The pulmonary arterial pressure and pulmonary vascular resistance index were significantly lower in Group 1 than in Group 2. The aortic pressure and cardiac index did not differ significantly between the two groups. The wet-to-dry weight ratio and myeloperoxidase activity were significantly lower in Group 1 than in Group 2. CONCLUSIONS: These data suggested that inhaled nitric oxide improved early pulmonary function in living-donor lobar lung transplantation by vasodilatating the pulmonary vasculature and inhibiting neutrophil activation.

Establishment of a human hepatoma cell line, HLE/2E1, suitable for detection of p450 2E1-related cytotoxicity.

By transfection of an expression vector of human cytochrome P450 2E1 (CYP2E1) into a human hepatoma cell line (HLE), a new cell line (HLE/2E1) that stably expresses activity of CYP2E1 has been established. The HLE/2E1 cell line expressed a higher level of CYP2E1 messenger ribonucleic acid than did the mother HLE cell line. CYP2E1 enzyme activity determined by a p-nitrophenol oxidation assay was also higher in HLE/2E1 cells than in HLE cells. In addition, the enzyme activity of the HLE/2E1 cells was increased by ethanol treatment. Exposure to acetaminophen (APAP) or buthionine sulfoximine (BSO) caused a greater decrease in viability of the HLE/2E1 cells than that of the HLE cells, as determined by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay. The cytotoxicity of APAP or BSO to HLE/2EI cells was inhibited by the addition of ethanol or vitamin E. However, the cytotoxicity of both APAP and BSO was enhanced by 24-h preincubation of HLE/2E1 cells with ethanol. These results show that this cell line provides a useful model for studying catalytic properties of CYP2E1 and cytotoxic mechanisms of chemicals metabolized by CYP2E1.

[Five cases of pulmonary thromboembolism after chest surgery].

The incidence of pulmonary thromboembolism after chest surgery is increasing. Five cases of it in recent two years were described. Four cases were lung cancer, and the other was myasthenia gravis. All lung cancer cases were after left lobectomy, and the findings of thromboembolism were mainly detected in right lung. Though hypocapnia is characteristic of pulmonary thromboembolism, arterial blood gas tests did not show it in all cases. Slight hypoxemia and arrhythmia are noteworthy signs of pulmonary thromboembolism after chest surgery. As thrombolytic and anticoagulation therapy, urokinase and heparin were very useful in four of five cases. Four patients made a rapid recovery from pulmonary thromboembolism, but one died of cerebral hemorrhagic infarction. The other patient did not recover in spite of intense medication, extracorporeal membrane oxygenation, and pulmonary embolectomy. To prevent pulmonary thromboembolism after chest surgery, appropriate countermeasures should be considered.

The effects of recombinant tissue-type plasminogen activator (rt-PA) on canine cadaver lung transplantation.

The intrapulmonary thrombi that form after the cessation of circulation are thought to be one of the major causes of graft function failure. We evaluated the effect of recombinant tissue-type plasminogen activator (rt-PA) in a canine cadaver lung transplant model. Donor dogs were killed by the intravenous administration of pancuronium bromide without heparinization, and left for 2 h at room temperature. The donor lungs were then flushed with low potassium dextran glucose (LPDG) solution, being subjected to a total ischemic time of 3 h. Following left lung transplantation, the contralateral pulmonary artery of the recipient dogs was ligated. In group 1 (n = 6), chloride solution was administered from the main pulmonary artery for 90 min, commencing 15 min prior to reperfusion. In group 2 (n = 6), 2.5 microg/kg per min of rt-PA, and in group 3 (n = 6), 5.0 microg/kg per min of rt-PA, were continuously infused in the same manner as in group 1. Lung function, including arterial blood gases and pulmonary hemodynamics, was measured for 3 h. The side effects of rt-PA were evaluated by measuring the prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen, alpha2-plasmin inhibitor (alpha2-PI), plasminogen, and fibrin/fibrinogen degradation product (FDP). All of the animals in the three groups survived throughout the observation period. The group 3 animals had significantly better gas exchange than the group 1 animals, and the pulmonary hemodynamics were significantly better in the group 2 and 3 animals than in the group 1 animals. The FDP levels in the group 2 and 3 animals were significantly higher than those in the group 1 animals, while the PT and APTT were significantly prolonged in the group 3 animals. These findings led us to conclude that rt-PA improves early lung function, particularly pulmonary hemodynamics.

A case of thoracoscopic bilateral lung volume reduction surgery in a supine position.

We present a case of thoracoscopic bilateral lung volume reduction surgery performed with the patient in a supine position. By rotating the operative table, bilateral apical resection could be performed without difficulty. The duration of the operation was 160 minutes and the patient's forced expiratory volume in 1 second improved from 0.81 l to 2.49 l.

Partial liquid ventilation for acute allograft dysfunction after canine lung transplantation.

BACKGROUND: This study was designed to investigate the efficacy of partial liquid ventilation (PLV) on acute allograft dysfunction after lung transplantation. METHODS: The canine left lung allotransplantation model was used, with the graft preserved in 4 degrees C low-potassium dextran glucose solution for 18 hours. The control group (n = 6) had conventional mechanical ventilation, and the PLV group (n = 6) had perfluorooctylbromide instilled into the airway 30 minutes after reperfusion. For 360 minutes, allograft function and hemodynamics were evaluated. After the evaluation, myeloperoxidase activity of the graft tissue was assayed. RESULTS: All dogs survived for 360 minutes. In the PLV group, PaO2, shunt fraction, and alveolar to arterial gradient for O2 were significantly better than those in the control group after 120, 180, and 120 minutes, respectively (p < 0.05). After 240 minutes, peak airway pressure became significantly lower than that in the control group (p < 0.05). The PaO2 at 360 minutes was 102 +/- 55 mm Hg in the control group and 420 +/- 78 mm Hg in the PLV group (p < 0.0001), and the peak airway pressure was 21.4 +/- 4.1 mm Hg in the control group and 14.7 +/- 5.0 mm Hg in the PLV group (p < 0.05). Myeloperoxidase activity in the PLV group was lower than that in the control group. CONCLUSIONS: The study shows that PLV alleviated acute allograft dysfunction after lung transplantation.