Effects of pulmonary artery remodeling on pulmonary circulation after lung volume reduction surgery.

BACKGROUND: Significant pulmonary hypertension during exercise has been observed in patients with severe chronic obstructive pulmonary disease. Although favorable effects on pulmonary function and dyspnea symptoms have been demonstrated, the influence of lung volume reduction surgery (LVRS) on the pulmonary hypertension during exercise is still a controversial subject. METHODS: A pulmonary function test and 6-minute walking test were performed before and 3, 6, 12 and 24 months after LVRS (n = 12). Pulmonary hemodynamics at rest and during exercise was studied 6 months after operation. Morphology was examined in pulmonary arteries with external diameters of 100 - 200 micro m in the resected lung, and the wall thickness (defined as intima plus media) and percentage wall thickness (percentage wall thickness of the external diameter) of the pulmonary artery were calculated. RESULTS: LVRS improved early-phase pulmonary function and 6-minute walking distance. Although the increase in pulmonary capillary wedge pressure during exercise was significantly ameliorated, exercise pulmonary hypertension did not change after LVRS. The percent wall thickness was highly correlated with Delta Ppa (difference between mean pulmonary artery pressure at rest and mean pulmonary artery pressure during exercise) not only before, but also 6 months after LVRS. CONCLUSION: LVRS has no significant influence on exercise-induced pulmonary hypertension in patients with severe emphysema. From a histological analysis of the pulmonary artery in the resected lung, remodeling the pulmonary artery that may exist in the remaining lung is possibly one of the important factors preventing postoperative improvement in exercise pulmonary hypertension in patients with chronic obstructive pulmonary disease.

Vascular endothelial growth factor mRNA and protein expression in airway epithelial cell lines in vitro.

Vascular endothelial growth factor (VEGF) plays multifunctional roles in vascular permeability, repair and remodelling processes, in addition to the maintenance of vascular structure and function. In the present study, the potential of airway epithelial cell lines, BEAS-2B cells and A549 cells, to release and express VEGF in unstimulated and stimulated conditions was evaluated. The secretion and expression of VEGF were evaluated by enzyme-linked immunosorbant assay and by reverse transcriptase-polymerase chain reaction. The isoforms of released VEGF were determined by high-performance liquid chromatography. BEAS-2B cells and A549 cells released VEGF constitutively. Interleukin (IL)-1beta and tumour necrosis factor (TNF)-alpha augmented the release of VEGF in a time- and dose-dependent manner. The released VEGF was 165 amino acid residues in either condition. Pseudomonas aeruginosa lipopolysaccharide (LPS), interferon (IFN)-gamma, smoke extract (SE), neutrophil elastase (NE), and bradykinin stimulated the release of VEGF. Keracinocyte growth factor (KGF), which reduces vascular permeability, also stimulated both cells to release VEGF. VEGF messenger ribonucleic acid (mRNA) was expressed both time- and dose-dependently at 2 h, and declined after 2 h in response to IL-1beta and TNF-alpha. The expression of VEGF mRNA in airway epithelial cells was also augmented by LPS, IFN-gamma, SE, NE, and KGF stimulation. These data suggest that airway epithelial cells may regulate the maintenance of vascular structure and function, as well as vascular permeability, repair and remodelling processes, in a variety of lung conditions by expressing vascular endothelial growth factor.

Recurrence of thymoma: clinicopathological features, re-operation, and outcome.

BACKGROUND: Even after complete resection, recurrence of thymoma is not infrequently observed, and treatment of recurrent thymoma remains controversial. STUDY DESIGN: One hundred and twenty-six patients underwent surgically complete resection for thymoma, and 24 of them had a recurrence. Surgical treatment of recurrent thymoma was attempted in 15 patients for a total of 18 times. In the present study, the relevance of clinicopathological features and the re-operation on the survival rate after the recurrence were determined. RESULTS: The most frequent recurrent type was pleural dissemination (92%), with local recurrence observed in 5%. Overall 5- and 10-year survivals after recurrence were 37 and 16%, respectively. Disease-free interval after initial operation and complication of myasthenia gravis had no significant effect on postrecurrent survival. The use of postoperative mediastinal irradiation had no effect on reducing the recurrence rate or improving survival after recurrence. Two of 15 patients who underwent re-operation died of major complications after It. pleuropneumonectomy for severe pleural dissemination. In the present study, the re-operation was not significantly effective for prolongation of postrecurrence survival. CONCLUSION: Our study showed that re-operation should not be attempted for all patients with recurrent thymoma. Because effect of subtotal resection for severe pleural recurrence is disappointing, total resection for minimal pleural dissemination or small local recurrence will be undertaken to improve postrecurrent survival. Careful follow-up for > 10 years will increase the chance of the total resection of the recurrent thymoma.

Histamine stimulates alveolar macrophages to release neutrophil and monocyte chemotactic activity.

Histamine and serotonin are important inflammatory mediators in the pathophysiology of asthma, and asthmatic patients have higher plasma histamine and serotonin levels than non-asthmatic control subjects. Alveolar macrophages (AMs) synthesize and secrete a large number of substances that play a key role in acute and chronic inflammation including asthma. We postulated that AMs might release chemotactic activity for neutrophils and monocytes in response to histamine or serotonin. To test this hypothesis, bovine AMs were cultured, and the supernatant fluids were evaluated for neutrophil chemotactic activity (NCA) and monocyte chemotactic activity (MCA) by a blind well chamber technique. AMs released chemotactic activity in response to histamine and serotonin in a dose- and time-dependent manner (P <.05). Partial characterization and molecular sieve column chromatography revealed that low-molecular-weight lipid-soluble activity was predominant. Lipoxygenase inhibitors significantly blocked the release of chemotactic activity. Leukotriene B(4) receptor antagonists blocked the chemotactic activity. Immunoreactive leukotriene B(4) significantly increased in supernatant fluids in response to histamine and serotonin. The receptor responsible for the release of chemotactic activity in response to histamine was the H2 receptor. These data demonstrate that AMs release NCA and MCA in response to histamine or serotonin (or both) and may modulate the inflammatory cell recruitment into the lung.

Pulmonary epithelioid hemangioendothelioma coexistent with pulmonary metastasis of thyroid cancer.

We report a 45-year-old man with epithelioid hemangioendothelioma (EH) and simultaneous pulmonary metastasis of thyroid cancer in his lung. Thyroid cancer, and multiple small nodules in both lungs were noted. He underwent total thyroidectomy followed by radiotherapy with 131I. However, 131I scintigraphy showed poor uptake of radionuclide in the nodules, and the size of the nodules remained unchanged. The diagnostic thoracoscopic biopsy showed two types of nodules, some were positive for thyroglobulin and cytokeratin, and others were reactive for factor VIII. The former nodules were diagnosed as pulmonary metastases of thyroid cancer, and the latter EH.

[Clinical study of operated nine thymic carcinomas].

Nine cases of thymic carcinoma (5 males and 4 females) were operated in our hospital between 1990 and 1998. These cases included 4 squamous cell carcinomas, 2 small cell carcinomas, 2 undifferentiated carcinomas and one adenocarcinoma. Preoperative chemotherapy were performed in 3 cases. All cases underwent median-sternotomy followed by mediastinal irradiation, 4 had total resection of the tumor, 2 had subtotal resection and 3 had exploratory thoracotomy followed by mediastinal irradiation. Adjuvant chemotherapy were administered in 4 cases and re-operation were performed in 2 cases. We applied Masaoka's clinical staging for thymoma, nine cases consisted of 6 stage III cases, 2 stage IV b cases and one stage IV a case. Within 2 years after operation, 3 cases (two complete resection cases and one exploratory thoracotomy case) were died of the carcinoma. However, two cases of squamous cell carcinoma have been alive more than 5 years after surgery followed by chemoradiation. The remaining 4 patients are alive either with or without the carcinoma after 7 to 28 months after operation. Thymic carcinoma is not so common mediastinal tumor but is expected to increase in the future. The treatment of thymic carcinoma remains a controversial matter and the survival is poor compared with invasive thymoma, but multimodal-therapy would contribute to improvement of the results in treatment for thymic carcinoma especially in squamous cell carcinoma.

Results of three-year mass screening programme for lung cancer using mobile low-dose spiral computed tomography scanner.

The aim of this study was to evaluate the usefulness of annual screening for lung cancer by low-dose computed tomography (CT) and the characteristics of identified lung cancers. Subjects consisted of 5483 general population aged 40-74 years, who received initial CT scans in 1996, followed by repeat annual scans for most subjects in 1997 and 1998, with a total of 13 786 scans taken during 1996-1998. Work-up examinations for patients with suspicious lesions were conducted using diagnostic CTs. The initial screening in 1996 detected suspicious nodules in 279 (5.1%) of 5483 subjects, and 22 (8%) were confirmed surgically to have lung cancer. Corresponding figures in 1997 and 1998 screening studies were 173 (3.9%) of 4425 and 25 (14%) of 173, and 136 (3.5%) of 3878 and 9 (7%) of 136, respectively. The sensitivity and specificity of detecting surgically confirmed lung cancer were 55% (22/40) and 95% (4960/5199) in 1996 and 83% (25/30) and 97% (4113/4252) in 1997 screening, respectively. 88% (55/60) of lung cancers identified on screening and surgically confirmed were AJCC stage IA. Our trial allowed detection of nearly 11 times the expected annual number of early lung cancers. Repeat CT allowed the detection of more aggressive, rapidly growing lung cancers, compared to those in the initial screening.

[A case of intrathoracic schwannoma derived from the left vagus nerve].

We report a case of schwannoma asymptomatic for 9 years, derived from the left vagus nerve in the middle mediastinum. This spindle-shaped tumor caused paralysis of the left recurrent nerve as an initial clinical manifestation with cough. T2-weighted magnetic resonance imaging (MRI) showed a neurogenic tumor with a characteristic target appearance and with constituents of different intensities: mucinous material in the peripheral zone and solitary tissue in the central zone. But, this different intensity is not directly reflected by the histopathologic features of Antoni types A and B. These findings suggest that MRI is useful for determining the parent nerve of a neurogenic tumor and is helpful for the diagnosis.

[Assessment of the new TNM classification for resected lung cancer].

To evaluate the revised TNM classification, we investigated the prognoses of 552 consecutive patients who had resection of non-small-cell lung cancer between April 1982 and March 1996. According to the new classification, the 5-year survival rate was 76.9% for stage I A, 57.2% for stage I B (I A versus I B, p < 0.0005), 47.7% for stage IIA, 49.8% for stage IIB, 18.6% for stage IIIA (IIB versus IIIA, p = 0.005), 16.7% for stage IIIB, and 7.9% for stage IV (IIIB versus IV, p = 0.02). Especially for patients in stage I A, there was significant difference in survival between patients with the tumor size within 1.5 cm and those with larger than 1.5 cm. The survival rate for T3N0M0 patients was significantly better than that for T3N1-2M0, but there was no significant difference between patients with T3N0M0 disease and those with T2N1M0 disease. Concerning the pm1 patients, the survival rate was significantly better than other stage IIIB patients. Our results supported the revision for dividing stage I and putting T3N0M0 into stage IIB. However, the classification is controversial about dividing stage II and putting pm1 as T4 disease. Furthermore, subgrouping of T1N0M0 disease by tumor size, T3 by tumor invaded organ will be necessary in the next revisions.

Intrapleural rupture of a cystic thymoma.

Although cystic degeneration of a thymoma is not uncommon, rupture of a cystic thymoma is rare. The authors report a patient with sudden chest pain and dyspnea due to rupture of a cystic thymoma into the right pleural space.

Solitary aneurysm of the innominate vein.

Two cases of isolated saccular aneurysms of the innominate vein are presented that appeared as mediastinal masses. Contrast-enhanced computed tomography (CT) allowed for accurate diagnosis in one patient, while the second patient had atypical CT findings that led to thoracotomy for proper diagnosis. A diagnosis of innominate vein aneurysm should be considered when a uniform attenuation mediastinal mass is seen on CT so that unnecessary biopsy and surgery can be avoided.

Pulmonary artery remodeling modifies pulmonary hypertension during exercise in severe emphysema.

To clarify the relation between the vessel remodeling and the physiology of pulmonary circulation in chronic obstructive pulmonary disease (COPD), we studied the pulmonary hemodynamics at rest and during exercise (25W) and the morphology of pulmonary arteries with external diameters of 100-200 microm in ten patients with severe emphysema. The wall thickness (WT) was defined as the intima plus media. The percent WT of the external diameter (% WT) in emphysema (36.0 +/- 4.3%) was significantly increased compared with that (22.6 +/- 3.3%) in five control lungs. The % WT was not related to pulmonary arterial pressure (Ppa) at rest, but was highly correlated with exercise Ppa (r = 0.721, P = 0.02) and with deltaPpa (Ppa during exercise-Ppa at rest) (r = 0.899, P = 0.0004). These findings suggest that pulmonary artery remodeling leads to reduced recruitability and distensibility of pulmonary vessels and is closely related to exercise pulmonary hypertension.

Different effects of lung volume reduction surgery and lobectomy on pulmonary circulation.

OBJECTIVE: To clarify the effects of lung volume reduction surgery (LVRS) on cardiopulmonary circulation during exercise in comparison with pulmonary lobectomy for lung cancer. SUMMARY BACKGROUND DATA: LVRS improves pulmonary function and dyspnea symptoms acutely in selected patients with heterogeneous emphysema. However, there are few data concerning the effects of LVRS on the cardiopulmonary circulation, especially during exercise. METHODS: Pulmonary function tests and pulmonary hemodynamic study at rest and during exercise were performed before and 6 months after LVRS (seven patients) or pulmonary lobectomy (eight patients). In the workload test, an electrically braked bicycle ergometer (25 w) was used in the supine position for at least 2 minutes or until exhaustion or breathlessness developed. RESULTS: After lung lobectomy, the values of vital capacity, percentage of predicted vital capacity, forced expiratory volume in 1 second, percentage of predicted forced expiratory volume in 1 second, residual volume/total lung capacity, and maximal voluntary ventilation deteriorated significantly. Six months after LVRS, however, vital capacity, percentage vital capacity showed no significant change, and forced expiratory volume in 1 second, percentage of forced expiratory volume in 1 second, diffusing capacity for carbon monoxide, and maximal voluntary ventilation showed marked improvement. Cardiac index was changed neither at rest nor during exercise in either group by the operation. Although postoperative pulmonary arterial pressure in the lobectomy group was significantly increased by the exercise, LVRS did not affect postoperative pulmonary arterial pressure at rest or during exercise. Pulmonary capillary wedge pressure in the lobectomy group showed no significant change after the operation, whereas LVRS ameliorated the marked elevation of pulmonary capillary wedge pressure observed during exercise. After lobectomy, significant increases in the pulmonary vascular resistance index were observed at rest and during exercise. LVRS markedly increased the pulmonary vascular resistance index at rest but not during exercise. In the lobectomy group, the postoperative flow-pressure curve moved upward, and its gradient became steeper than the preoperative one. In the LVRS group, the curve moved upward in a parallel fashion. These results show that much more right-sided heart work is needed to achieve the same cardiac output against higher pulmonary arterial pressure, not only after lobectomy but also LVRS. CONCLUSION: The current study demonstrated that the effects of LVRS on the cardiopulmonary circulation were not negligible, especially during exercise, and successful LVRS may depend on improved respiratory function and also preserved cardiac function that can tolerate the damage to the pulmonary vascular bed induced by this operation.

[Two cases of the bronchial cyst located in the anterior mediastinum].

Bronchial cysts are common cystic tumors around the tracheobronchial tree in the middle and posterior mediastinum and rarely locate in the anterior mediastinum. We reported two cases of the bronchial cyst located in the anterior mediastinum. One case was a 57 year-old-female. A thymic cyst was suspected and the extended total thymectomy was performed through the mediansternotomy. The microscopic examination showed bronchial epithelium and cartilage in the cystic wall. The another case was 71 year-old-male operated by thoracoscopic surgery for the cystic tumor in the anterior mediastinum. Microscopic examination showed bronchial epithelium and gland in the cystic wall.

[A case of thymic carcinoid with multiple endocrine neoplasm (MEN)-type I].

We presented a case of thymic carcinoid with MEN type I. A 43-year-old woman who followed at MEN type I for 4 years was pointed out an abnormal shadow by chest X-ray. Chest CT levealed the presence of two anterior mediastinal tumors. Extended total thymectomy was performed through the median sternotomy. There were 3 tumors in thymus. Histological examination revealed three tumors in the thymus and all of the tumor were diagnosed carcinoid. Our experience suggests that CT or MRI of the chest should be considered as part of clinical screening in patients with MEN type I.

Longterm effects of pulmonary resection on cardiopulmonary function.

BACKGROUND: Major lung resection decreases ventilatory capacity and reduces exercise tolerance, impairing postoperative quality of life. But we have often seen respiratory symptoms improve during several years of postoperative followup. In the current study, we evaluated postoperative changes in cardiopulmonary function on exertion of patients with lung cancer surviving for more than three years, and the corresponding changes of their respiratory symptoms. METHODS: The effects of pulmonary resection on cardiopulmonary function were evaluated in eight patients with lung cancer. Pulmonary function tests and hemodynamic study at rest and during exercise were performed before, in the early (4 to 6 months) and late (42 to 48 months) postoperative phases after major lung resection. RESULTS: None of the eight patients had any remarkable symptoms before lung resection. In the early postoperative study, the general condition of five patients deteriorated compared with their preoperative status. In the late postoperative study, four patients showed an improvement of their daily activities from the early postoperative phase. Pulmonary function in the late postoperative phase did not show major changes except for airway resistance and percentage of carbon monoxide diffusing capacity as compared with the early phase, which showed deterioration as compared with the preoperative period. Cardiac index and stroke volume index were significantly decreased during exercise on maximal effort in the late postoperative phase compared with other phases. These results suggest that the peak blood flow per unit of remaining lung during exercise becomes lower with time after lung resection, indicating deterioration of the condition of the pulmonary vascular bed. The deterioration was also revealed from the pressure-flow curve. CONCLUSIONS: The condition of the pulmonary vascular bed after major lung resection does not improve, even in the late postoperative phase, although clinical symptoms were sometimes improved compared with the early postoperative period.

L-arginine inhibits ischemia-reperfusion lung injury in rabbits.

BACKGROUND: Recent studies have reported that nitric oxide (NO) acts as a cytoprotective mediator in ischemia-reperfusion (IR) lung injury. We hypothesized that the addition of L-arginine to the perfusate would attenuate the increases in microvascular permeability and pulmonary vascular resistance. MATERIALS AND METHODS: Isolated rabbit lungs were reperfused for 60 min after 120 min warm ischemia. Lung injury was assessed using the fluid filtration coefficient (Kf), pulmonary vasucular resistance (PVR) before ischemia and after reperfusion, and a wet-to-dry lung weight ratio (W/D). RESULTS: The Kf of the control group (without L-arginine) was significantly increased after reperfusion. Lungs perfused with L-arginine showed attenuation of the IR-induced increases in Kf and PVR. Addition of Nomega-nitro-L-arginine (L-NA), a NO synthase inhibitor, to the perfusate reduced the beneficial effects of L-arginine. The lungs perfused with dibutyryl-cyclic GMP (dbcGMP) showed attenuation of IR-induced increases in Kf and PVR. There were no significant differences in the W/D ratio between these groups. CONCLUSIONS: These results demonstrate that L-arginine has beneficial effects on IR lung injury, perhaps due to enhancement of endothelial cGMP levels.

Improvements in thoracic movement following lung volume reduction surgery in patients with severe emphysema.

In twelve patients with severe emphysema who underwent lung volume reduction surgery (LVRS), we assessed the results of dyspnea scale, pulmonary function, 6-minute walk distance (6MD), and thoracic movement prior to and 6 months following LVRS. Postoperatively, forced expiratory volume (FEV1), maximum inspiratory mouth pressures (MIP), maximum expiratory mouth pressures (MEP), maximum voluntary ventilation (MVV), diffusing capacity for carbon monoxide (DLCO), partial pressure of oxygen (PaO2) and 6MD were significantly increased with the decrease in dyspnea scale and lung hyperinflation. Thoracic movement, as assessed by the bilateral lung area ratio of the mid-sagittal dimension of dynamic magnetic resonance imaging (MRI) at full inspiration to that at full expiration, was significantly increased. The improvement in thoracic movement was significantly correlated with the increases in FEV1, MVV, and MIP, and with the decrease in residual volume (RV), and with the improvement in the dyspnea scale. These findings suggest that LVRS is an effective procedure for improving not only the airflow limitation and gas exchange but also the thoracic movement in severe emphysema, and these improvements may contribute to an increase in exercise performance and relief of dyspnea.

[Catamenial pneumothorax under video-assisted thoracoscopic surgery: a case report].

A 46-year-old woman complained four times of chest pains due to repeated right pneumothorax. This was improved by the right thoracic drainage each time. She was diagnosed as having catamenial pneumothorax from the fact that each episode of pneumothorax began with the first day of her menstrual cycle. She was admitted to our hospital in Jan. 1996 and operated on by the obliteration of pleuro-peritoneal fistulas on right diaphragm under video-assisted thoracoscopic surgery (VATS). No other abnormal lesions were found in the right pleural cavity and right lung. In this case, the pathophysiological mechanisms of pneumothorax might have been caused by the air influx from the peritoneal cavity to the right pleural cavity through the fistulas on the right diaphragm. VATS is minimally invasive surgery and very useful for the treatment of pleuro-peritoneal fistulas on the diaphragm. It should be emphasized that hormonal therapy is necessary after VATS of catamenial pneumothorax.

Intrapulmonary metastasis of lung cancer: soft x-ray investigation of inflated and fixed lung.

BACKGROUND: Intrapulmonary metastasis (IPM) of lung cancer is thought to be an important factor influencing patient prognosis. It is not easy to detect a small IPM by preoperative examination and sometimes even by postoperative pathologic investigation. We applied soft x-ray investigation to inflated and fixed lungs for the detection of IPM. STUDY DESIGN: From 1990 to 1992, 75 patients with lung cancer who had no metastatic lesions on preoperative whole CT, MRI, and technetium-99m bone scintigram examinations underwent lung resection. The resected lungs were fixed in an inflated condition, sliced at the corresponding CT levels into 10-mm-thick sections, and submitted for soft x-ray examination. When an accessory nodular shadow(s) was detected on the soft x-ray images, the size of the nodule and its distance from the primary tumor were measured. RESULTS: In 23 of the 75 patients, accessory nodular shadows were detected on the soft x-ray images. Six nodules in 6 patients proved to be IPM, 2 of which were also detected by postoperative macroscopic examination. Another 2 microscopic IPM were found only by postoperative pathologic examination. The total detection rate of IPM was 10.7% (8 of 75 patients) in this series. The detection rate of IPM at our institute was 5.4% before this study (1979 to 1989). The mean diameter of the IPM detected by the soft x-ray method was 2.8 +/- 1.5 mm, and this was significantly smaller than that of the macroscopically detected nodules (7.2 +/- 3.2 mm). CONCLUSIONS: Our data show that soft x-ray investigation is an effective procedure to detect relatively small intrapulmonary metastatic nodules and will contribute to precise postoperative staging of patients with lung cancer.