Efficacious pleurodesis with OK-432 and doxorubicin against malignant pleural effusions.

Malignant pleural effusion develops frequently in patients with advanced lung cancer. Chemical pleurodesis is the most effective palliative treatment for these patients. The efficacy of pleurodesis using both OK-432, a preparation of Streptococcus pyogenes, and doxorubicin for 20 patients with cytology-proven malignant pleural effusion associated with lung cancer was evaluated. After complete removal of pleural effusion, OK-432 and 30 mg of doxorubicin were injected via an inserted chest tube. Treatment was terminated when the volume of daily drainage reached <200 mL. If the daily volume remained >200 mL, an additional OK-432 was administered every 3 days. In total, 16 patients (80%) revealed a complete response, two patients (10%) revealed a partial response, and no response was seen in two patients. Eighteen patients with complete or partial responses did not show subsequent reaccumulation of pleural effusion after pleurodesis. The chest tube remained in place for an average of 6.4 days, draining a mean of 2,854 mL. The main side-effects were fever and pain that were easily treated with nonsteroidal anti-inflammatory drugs. Pleurodesis using both OK-432 and doxorubicin showed high efficacy for controlling malignant pleural effusions caused by lung cancer.

[True pulmonary carcinosarcoma suspected as a metastatic lung tumor].

This patient, a 53-year-old man, has underwent operation on the diagnosis of esophageal cancer 2 years ago. An abnormal shadow was detected in the left lung field and he was admitted to our hospital for further examination. On the suspicion of metastatic lung tumor by transbronchial brushing cytology, partial resection of the left lower lobe was performed. Histologically the tumor was of carcinomatous (squamous cell carcinoma and adenocarcinoma) and sarcomatous (fibrosarcoma and chondrosarcoma) elements, so the patient was diagnosed as "true" pulmonary carcinosarcoma. True pulmonary carcinosarcoma is one of the very rarest neoplasms of the lung.

[A clinicopathological study of pulmonary cryptococcosis--chest CT and pathologic correlation].

We reviewed the clinicopathological features in 12 patients (7 males and 5 females; mean age 54 yr) with pulmonary cryptococcosis. Eleven of the patients were asymptomatic and the disease was detected by chest radiograph abnormalities. The underlying systemic disease had been diagnosed as diabetes mellitus in two. Chest CT scans showed a solitary nodule in 9 of the 12 patients, multiple nodules in 2, and infiltration in 1. The nodular diameter was less than 2 cm in 10 of the 12. All nodules were located in the subpleural region. On the chest CT, cavitary nodules, scattered nodules, or both, and spiculated nodules were difficult to distinguish from pulmonary tuberculosis and primary lung cancer, respectively. According to McDonnell's pathological classification of pulmonary cryptococcosis, the resected 8 lungs revealed peripheral pulmonary granuloma in 5 and granulomatous pneumonia in 3. It is important to perform a pathological examination for the diagnosis of pulmonary cryptococcosis to avoid misdiagnosis as lung cancer or pulmonary tuberculosis.

[Exogenous lipoid pneumonia induced by inhalation of insecticide].

We report a case of exogenous lipoid pneumonia induced by insecticide. A 67-year-old man was admitted to our hospital with complaints of dyspnea cough, hemoptysis, and shivering 6 hours after inhaling an insecticide. A chest radiograph on admission disclosed consolidation in the right upper lobe. Chest computed tomography showed nodular infiltrates associated with ground-glass opacities. Bronchoalveolar lavage fluid was hemorrhagic and showed neutrophilia. Pathological examination of transbronchial lung biopsy specimens showed numerous vacuolated macrophages in alveolar spaces. Electron microscopy demonstrated lipid droplets in the cytoplasm of these macrophages. These findings together yielded a diagnosis of exogenous lipoid pneumonia induced by insecticide. In addition, we experimentally induced a similar form of lipoid pneumonia in rats by intratracheal instillation of the same insecticide.

Successful treatment of refractory bronchorrhea by inhaled indomethacin in two patients with bronchioloalveolar carcinoma.

Bronchorrhea in patients with bronchioloalveolar carcinoma is not uncommon. However, to our knowledge, an effective treatment for bronchorrhea in these patients has not been established. Recently, we have confirmed the efficacy of inhaled indomethacin in severe refractory bronchorrhea in comparison to that of other medications in two patients with bronchioloalveolar carcinoma. Despite the administration of a macrolide and corticosteroid, sputum volume increased to 700 mL/d in case 1 and to 200 mL/d in case 2 and hypoxemia and dyspnea deteriorated. Within a few days after the initiation of treatment with inhaled nebulized indomethacin (75 mg/d), sputum volume started to decrease and was controlled to < 100 mL/d, associated with alleviation of dyspnea and hypoxemia. To our knowledge, this is the first report of successfully treated refractory bronchorrhea associated with bronchioloalveolar carcinoma by inhaled indomethacin, resulting in markedly reduced sputum volume, improved quality of life, and prolonged survival.

[Pulmonary vein reconstruction for lung carcinoma].

Four cases of primary lung carcinoma (two squamous cell carcinomas and two adenocarcinomas) were performed right middle lobectomy combination with the reconstruction of upper pulmonary vein to remain the upper lobe. Lung carcinomas were in the right lobe and infiltrated to lower margin of upper pulmonary vein in all cases. After resection of the right middle lobe and an affected portion of upper pulmonary vein, the defect of the upper pulmonary vein was replaced with auto-pericardial graft in three cases, and the other one was closed by continuous suture of 5-0 plorene. Pathological classification of these four cases was stage IB in one patient, stage IIB in two and stage IV in one. All patients died from 6 to 53 months after operation (average: 31 months). Metastasis to distant organs was confirmed in all cases, so the prognosis of them was generally poor. Reconstruction of pulmonary vein may be feasible to avoid over resection of other lobes, because pulmonary function can be preserve as well as in the bronchoplasty.

Bronchiolitis in Kartagener's syndrome.

The association of diffuse bronchiolitis in patients with Kartagener's syndrome (KS) has not been reported previously. The aim of this study was to present the morphological characteristics of bronchiolitis in patients with KS. Eight patients (four males, four females; mean age 37.9+/-18.7 yrs), clinically diagnosed as KS with the classical triad of chronic pansinusitis, bronchiectasis and situs in versus with dextrocardia, were evaluated. Routine chest radiography showed bronchiectasis and dextrocardia in all patients. Chest computed tomography (CT) showed diffuse centrilobular small nodules up to 2 mm in diameter throughout both lungs in six out of eight patients. Pulmonary function tests revealed marked obstructive impairment in all patients (forced expiratory volume in one second 57.0+/-11.3%, residual volume/total lung capacity 45.+/-12.7%, maximum midexpiratory flow 0.92+/-0.72 L x s(-1), forced vital capacity 74.1+/-12.2% (all mean +/- SD)). The examination of cilial movement of the bronchus revealed immotility in all of the five patients examined. The ultrastructure showed ciliary dynein arm defects in all patients. Histopathological examination of lung specimens obtained at autopsy or by video-assisted thoracoscopic surgery showed obliterative thickening of the walls of the membranous bronchioli with infiltration of lymphocytes, plasma cells and neutrophils, but most of the distal respiratory bronchioli were spared and alveolar spaces were overinflated. Pathologically, the diffuse centrilobular small nodules on the chest CT mainly corresponded to membranous bronchiolitis. This is the first report demonstrating that the association of diffuse bronchiolitis might be one of the characteristic features of the lung in Kartagener's syndrome.

[Combination chemotherapy with continuous infusion of low-dose cisplatin and UFT for advanced non-small cell lung cancer].

A combination chemotherapy with continuous infusion of cisplatin (5 mg/body, day 1-5) and UFT (400-600 mg/body, day 1-5) was administered to thirteen patients for advanced non-small cell lung cancer. Myelosuppression and other toxicity were mild, and the quality of life of the patients was good. The response rate of thirteen patients was 23% (CR 0, PR 3). It was considered that chemotherapy using cisplatin (5 mg/body, day 1-5) and UFT (400-600 mg/body, day 1-5) was well tolerated and effective for the treatment of non-small cell lung cancer.

Diffuse panbronchiolitis in rheumatoid arthritis.

The association of progressive obliterative bronchiolitis (OB) with rheumatoid arthritis (RA) is uncommon but has been reported previously. Diffuse panbronchiolitis (DPB) is a unique inflammation principally affecting the respiratory bronchioli and has been reported mainly in Japanese adults. Recently, DPB has also been noted in patients with RA in Japan. Therefore, there might be considerable overlap in clinical features between DPB and OB associated with RA in Japan. The aim of this study was to evaluate the clinicopathological characteristics of bronchiolitis in patients with RA. Three RA patients clinically diagnosed as having DPB were evaluated. All patients underwent chest radiographs, pulmonary function tests (PFT) and post mortem examination. Clinical features in all patients were a history of productive cough, exertional dyspnoea, wheezing and/or coarse crackles. Chest radiographs showed small nodular shadows up to 2 mm in diameter with bronchiolectasis throughout both lungs in all patients. The PFT revealed marked obstructive impairment in all patients. All patients died of progressive respiratory failure. Pathologically, two out of the three cases were confirmed as DPB, while the remaining one case was confirmed as OB, because the primary obstructive lesions were in the respiratory bronchioli in the former and in the membranous bronchioli and the proximal small bronchi in the latter. Thus, the clinical features of DPB and OB were strikingly similar, but the histopathological features revealed distinct differences. This study demonstrated that there was considerable overlap in clinical features between diffuse panbronchiolitis and obliterative bronchiolitis associated with rheumatoid arthritis, suggesting that diffuse panbronchiolitis might be a new manifestation of rheumatoid arthritis. The differentiation of these two disease entities is significant in making decisions on their therapeutic modality and is possible by analysing the precise histopathological findings of the lung.

[A case of medullary carcinoma of the thyroid gland: metachronous bilateral metastasis of the neck and mediastinal lymph nodes were treated successfully by staged resection].

This patient, a 52-year-old male, underwent subtotal thyroidectomy on the diagnosis of medullary carcinoma of the thyroid gland in 1980 and postoperative course was uneventful. Since November 1990 he had a persistent diarrhea for 6 months and was admitted to the hospital for the further examination on June 1991. The serum CEA and calcitonine level was very high and chest CT scan findings showed the swelling of right neck and mediastinal lymph nodes. Dissection of the lymph nodes was performed by anterior approach which was gained through a proximal median sternotomy extended into the anterior fourth intercostal space as well as to the base of the neck on the right side. On the pathological examination it was metastasis of medullary carcinoma of the thyroid gland. And 50 months later after second operation he had a persistent diarrhea once again. Left neck and mediastinal lymph node metastasis was detected by chest CT with high serum CEA and calcitonine level. Similarly resection was performed by the same anterior approach on the left side. Irrespective of the extended resection he was free of severe complication; he is still alive 10 months after the third operation without any evidence of recurrence and his current performance status is very good.

[Lymphocytic interstitial pneumonia associated with Sjögren's syndrome and mediastinal lymphadenopathy: diagnosis by open-lung biopsy].

A 56-year-old woman was admitted to the hospital because of dry coughing and shortness of breath on exertion. In addition, dry eyes and cornea guttata suggested Sjögren's syndrome. Chest radiography revealed linear, reticular shadows throughout the lung fields, and enlargement of hilar and mediastinal lymph nodes. A specimen was obtained by transbronchial lung biopsy but the findings were not condusive; open-lung biopsy was done. The histopathological findings suggested lymphocytic meterstitial pneumonia. Results of genetic analysis and of immuno-histochemical examination conformed that the proliferating lymphocytes were polyclonal. Corticosteroids and immunosuppressive drugs have been used to treat lymphocytic interstitial pneumonia, and they were effective in this case.

[Assessment of surgery for primary lung cancer with dissemination or malignant effusion of pleura (T4 advanced lung cancer)].

Twenty-four cases of primary lung cancer with dissemination or malignant effusion of pleura detected preoperatively or intraoperatively were surgically treated at our hospital. Mean survival time (MST) and two-year survival rate (2 YSR) were analyzed on their resected cases and non-resected cases with similar lesion. MST and 2 YSR of 19 cases with lobectomy, 5 cases with pneumonectomy including pleuropneumonectomy and 15 cases with no surgical procedure were 2.77 +/- 0.60 years, 53.4%, 1.51 +/- 0.50 years, 26.7% and 0.99 +/- 0.15 years, 6.7%. MST and 2 YSR of 13 cases with lymph node dissection under R 1 and 6 cases over R 2 on lobectomy group were 1.99 +/- 0.38 years, 37.5% and 5.66 +/- 1.71 years, 66.7%. These findings suggested that lobectomy with lymph node dissection of R 2 over may be a beneficial treatment of lung cancer with dissemination or malignant effusion of pleura.

[A case of lung adenocarcinoma: detection and resection of the metastatic lesion was managed effectively by serum CEA level].

This patient, a 53-year-old male, has had back pain and an abnormal shadow was detected in the right lung field on December 1989. He was admitted to the hospital for the further examination. On the diagnosis of lung cancer with high serum CEA level operation was performed on February 1990. As a results of pathological examination, histological type was adenocarcinoma and pathological stage was pT3N0M0 stage IIIA. After operation the serum CEA level was decreased immediately but it was gradually increased once again. And then 14 months later right adrenal metastasis was detected by abdominal CT with high serum CEA level and resection was performed. Similarly a solitary lymph node metastasis located in abdomen was detected and resected with high serum CEA level 28 months after second operation. In this case detection and resection of the metastatic lesion was managed effectively by serum CEA level. The patient had a good operative course and is alive 76 months after first operation without any evidence or recurrence.

Bronchoscopic findings of extramural lung cancer invading the subepithelium or submucosa.

Bronchoscopic findings from the main to segmental bronchi were compared with the histopathological findings in 185 resected cases of lung cancer, in order to determine which bronchoscopic features are associated with lung cancer invading the subepithelium or submucosa from beyond the bronchial wall. Carcinoma invaded the subepithelium or submucosa from beyond the bronchial wall in 43 cases (22.9%) out of the total of 185 cases. Bronchoscopic findings were evaluated in these 43 cases, and were summarized as follows: (1) The bronchoscopic findings in cases of subepithelial invasion consisted of vascular engorgement, bleeding, subepithelial tumor, and emphasized longitudinal relief; (2) irregularity of the mucosa was observed in cases of epithelial or muscular invasion; (3) indistinct bronchial cartilage was observed in cases of invasion proximal to the extramuscular layer; (4) accentuated irregular folds were observed in cases of invasion of the extramuscular or cartilage layers; and (5) edema and redness were not specific for malignancy. In addition, the occurrence of mediastinal lymph node metastasis was higher in cases of invasion to main or lobar bronchi. This result indicates that recognition of invasion of the subepithelium or submucosa of the central bronchus may be helpful in indicating the probability of mediastinal lymph node metastasis. Accordingly, there may be specific bronchoscopic findings which correlate with invasion of the bronchial subepithelium or submucosa. Accurate recognition of these findings may be useful in determining appropriate biopsy sites and may provide more information concerning selection of therapeutic strategy.

[The duty of hospice for holistic medicine].

The hospice program has a sense of absolute in the context of the provision of treatment by the medical establishment. The aim of the medical establishment is humanistic treatment. The aim of the hospice program is to allow doctors in charge, thru their medical skills, to make the most effort for the life of the patient. As such, the goal of the hospice program is not just to ease the physical pain of terminal patients, but rather to help the patient live the remainder of his or her life in a meaningful way, offering intensive support and energy to help the patient challenge and even defy his or her life. Today in Japan, the hospice care program has established a system of renumeration for use of special cancer wards and pain-easing treatments. Because of this, hospice care is becoming wide-spread among medical care organizations. Such wide-spread care is a very desirable thing. But if the economic value of hospice care is only to ease physical pain, then hospice care is essentially a formless act. If we do not effect the appropriate value both socially and economically, one wonders if the hospice care in Japan will be able to develop the correct approach.

Serum neuron specific enolase level as a prognostic factor in non-small cell lung cancer.

In 93 patients with inoperable non-small cell lung carcinoma who underwent chemotherapy including cisplatin, the prognostic value of 9 factors were determined using Cox's proportional hazard model. Univariate analysis revealed that patients with a performance status of grade 2 (p < 0.01) or 3 (p < 0.05), those with stage IV disease (p < 0.05), those with a serum neuron specific enolase (NSE) level > 7.0 ng/ml (p < 0.001), and those with a low serum albumin level (p < 0.05) had a significantly worse prognosis. Multivariate analysis showed that a performance status of 2 or 3 and a high NSE serum level were associated with a significantly worse prognosis. More attention should be paid to the serum NSE level in patients with non-small cell lung carcinoma, because it not only reflects the tumor volume, but is also a prognostic factor which is dependent on individual tumor characteristics.