Recently, the measurement of tumor markers, particulary for combined measurement, have been reported to be useful for the early diagnosis of cancer. In this study, the authors measured the serum levels of SLX, CA19-9 CA153, CA125, NCC-ST-439, CEA, SCC, NSE, TPA and IAP in 155 patients with primary lung cancer before treatment (76 adenocarcinomas, 40 squamous cell carcinomas, 36 small cell cancers, 3 large cell cancers). Seventy three benign lung disease cases were also studied as controls. The serum levels of CA19-9, CA153, CA125, NCC-ST-439, CEA, NSE and TPA were significantly higher in lung cancer patients than in benign lung disease patients. CA125 and CEA levels in adenocarcinoma, SCC levels in squamous cell carcinoma, NSE levels in small cell cancer and NCC-ST-439 in non-small cell cancer were significantly higher than those of other histological types of cancer. The level of each marker became higher, and was related with advance in stage. The probability of lung cancer was 90% when three markers were positive except for IAP, which was frequently false positive in benign lung disease.
In conclusion, the simultaneous, combined measurement of at least three markers, including CEA and/or TPA was considered to be useful for the diagnosis of lung cancer.

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To elucidate the predisposing factors of terminal pulmonary infection in patients with lung cancer, we reviewed the case record of 251 autopsy cases that died of lung cancer in Kyushu University Hospital from 1976 to 1987. The incidence of mycobacteriosis was significantly more frequent in cases treated with antineoplastic therapy and corticosteroid (Group III) than in those with antineoplastic therapy but without corticosteroid (Group II), while the incidence of common bacterial and nonbacterial infections was not significantly different between the two groups. In patients with lung cancer treated with antineoplastic therapy, corticosteroid administration of relatively short duration (less than a month) induced fatal mycobacteriosis. In cases with lymphocytopenia, the incidence of fatal mycobacteriosis was significantly more frequent in Group III than in Group II, whereas the incidence of fatal nonbacterial infection was not. In cases with monocytopenia, both fatal mycobacteriosis and nonbacterial infection were significantly more frequent in Grroup III than in Group II. In Group III, the incidence of mycobacterial and nonbacterial infections was not different significantly between cases with and without lymphocytopenia or monocytopenia. Thus, in patients with lung cancer, administration of corticosteroid has greater influence on the development and exacerbation of mycobacteriosis than lymphocytopenia or monocytopenia. On the other hand, the influence of certicosteroid on the development and exacerbation of nonbacterial infection was significantly different from that of lymphocytopenia. The administration of corticosteroid and antineoplastic therapy do not increase the incidence of terminal common bacterial infection in patients with lung cancer.

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In order to elucidate the therapeutic mechanisms of low dose-long term erythromycin (EM) therapy in patients with diffuse panbronchiolitis (DPB), the authors evaluated the effect of in vitro EM treatment on neutrophil (PMN) oxygen radicals production. EM has potent capacity to suppress PMN chemiluminescence (CL) induced by the N-formyl Met-leu-phe (FMLP), opsonized zymosan, and calcium ionophore A23187 stimulation. In marked contrast, phorbol myristate acetate (PMA)-induced PMN CL were much less affected by EM treatment. The suppressive activity of EM was dependent on the EM concentration and at a EM concentration of 25μg/ml, FMLP-induced PMN CL were suppressed by 45.3±5.6% (n=7), but PMA-induced CL were suppressed only marginally, 11.9±3.7% (n=7). The onset of inhibitory activity of EM is rapid and at 5min., 60.1% of the maximum suppression at 60 min. was observed. This EM-induced suppression was found to be reversible and dependent on the EM-pretreatment temperature since the suppressive activity of EM were observed only at 37°C but not at 0°C.These results suggest that actively transported intracellular EM exerts its suppressive activity by inhibiting the process of Ca⁺⁺ transfer or Ca⁺⁺ utilization by cells. In addition, these results were consistent with the concept that EM might act as an anti-inflammatory agent in chronic bacterial airway infections such as bronchiectasis and DPB where the PMN appear to play an important role in the generation of airway destruction.

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To analyze the immunological aspects of chronic respiratory tract infections, immunoglobulin G (IgG) subclass patterns were investigated in 20 patients with diffuse panbronchiolitis (DPB) and 20 patients with cystic bronchiectasis (CBE).
All IgG subclasses were increased in both diseases in comparison to the normal group. Increased levels of IgG₁ and IgG₂ were recognized more dominantly in DPB, whereas IgG₄ level was elevated in CBE.
Furthermore, analysis of the ratio of IgG subclass to total IgG showed increase of IgG₁ and decrease of IgG₂ in both diseases, and increase of IgG₄ only in CBE.
On the other hand, the increase of IgG₁ correlated with infection by P. aeruginosa while increase of IgG₄ was recognized in the group of non-P. aeruginosa infections.
These results indicate that increased IgG₁ and IgG₂ levels are common characteristic phenomena in chronic respiratory tract infections such as DPB and CBE, reflecting the pathophysiological aspects based on respiratory tract defense mechanisms against microorganisms, and demonstrated that differences of IgG subclass patterns are observed among DPB and CBE, and also according to causative agents.

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Asbestos exposure induces lung fibrosis, i. e. asbestosis, and furthermore, pathological changes of pleura, i. e. asbestos pleurisy of pleural plaque. Generally, asbestosis is induced by massive exposure to asbestos and pleural changes are induced by low dose exposure to asbestos.
The most important diseases which are induced by asbestos exposure are malignancies, especially malignant mesothelioma and lung cancer. Two cases, one malignant mesothelioma, the other lung cancer with asbestosis induced by asbestos exposure received almost the same dose of asbestos, as estimated from the period of asbestos exposure and occupational history and the same kind of asbestos (crocidolite) and had a smoking history. We do not know which elements may induce malignancies under asbestos exposure. Recently, some reports described that asbestos mediated the transformation of genes and this action induced malignancies. We should extend our study to the gene problem in cases of malignant mesothelioma and lung cancer induced by asbestos exposure.

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The plasma level of human DNA was determined by the dot-hybridization method using human Alu-family DNA as a probe in 45 patients with primary lung cancer, 54 patients with benign pulmonary diseases, and 59 healthy controls. The mean plasma DNA level was significantly higher in the patients with lung cancer than that in the patients with benign pulmonary diseases or in healthy controls. The mean plasma DNA level in the patients with benign pulmonary diseases was also significantly higher than that in healthy controls. There was no significant difference in mean plasma DNA level in each histologic type of lung cancer. The plasma DNA level was elevated above the cut-off level of 80ng/ml in 71% of the patients with lung cancer, 37% of the patients with benign pulmonary diseases and none of the healthy controls. The serum CEA was positive in 38% of the patients with lung cancer and thus when plasma DNA and serum CEA were used in combination, 78% of the cases with lung cancer could be detected by these two markers. In the patients with lung cancer who responded to treatment, the plasma DNA levels were significantly decreased after treatment, while its levels were elevated in the patients whose treatment was unsuccessful. These findings indicate that plasma DNA may be a useful marker in patients with lung cancer.

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An 82-year-old woman was admitted to Iwamizawa Rosai Hospital, Cardiovascular Medicine, for detailed examination of an aneurysm of abdominal aorta. CT scan revealed marked swelling of para-aortic lymph nodes which regressed spontaneously in three months. She was re-admitted to our hospital because of general malaise and gait disturbance. Her chest X-ray on the second admission revealed miliary disseminated shadows, which were confirmed to be tuberculous granuloma by lung biopsy. She was initially well controlled with anti-tuberculosis drugs, followed by severe liver dysfunction and pancytopenia, and died of respiratory and cardiac failure. At autopsy, wide-spread malignant lymphoma and miliary tuberculosis of the lung were found. The cause of liver dysfunction was strongly suspected to be due to infiltration of the lymphoma cells to portal triads of the liver. Hemophagocytosis found in the bone marrow, spleen and liver might be consistent with clinically so-called “hemophagocytic syndrome”, causing pancytopenia, associated with infection.

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Three family members who had worked as sandblasters in their own sandblasting factory showed innumerable small nodularities in both lung fields of their chest radiograms. One of those showed conglomerate shadows in the upper lung fields. Those shadows seemed to be consistent with those of silicosis. One of the patients was examined by transbronchial lung biopsy (TBLB) and showed typical silicotic nodules. Mineralogical studies were done on the abrasive particles and the deposited particles in the lung tissue specimen obtained via TBLB and bronchoalveolar lavage fluid sample (BALF) using polarized microscopy, X-ray diffraction and analytical electron microscopy. The particles which had accumulated on the floor of the factory mineralogically consisted of mostly (over 90%) silica quartz containing small amount of chlorite, and the deposited particles in the lung tissue and those in the BALF showed similar composition.

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A 44-year-old man was admitted for evaluation of dyspnea on exertion and subcutaneous nodules. The chest X-ray on admission revealed bilateral hilar lymph node swelling and diffuse micronodular shadows throughout both lung fields. Ga scintigram demonstrated diffuse abnormal uptake.
Serum angiotensin converting enzyme was elevated significantly (86.6 IU/l). The TBLB specimen confirmed the diagnosis of sarcoidosis. The cell numbers in bronchoalveolar lavage fluid was increased (4.4×108), the percentage of lymphocytes was elevated (64%) and the ratio of Leu 3a⁺/Leu 2a⁺ was very high (16.07). We further evaluated the spontaneous IL-1 release in vitro by alveolar macrophages obtained by bronchoalveolar lavage. The results showed that large amounts of IL-1 alpha and beta were produced spontaneously by alveolar macrophages before therapy, followed by a decrease in production after corticosteroid treatment. Previously, the authors reported that no significant amount of IL-1 alpha and beta was detected in 5 normal volunteers and 6 other active sarcoidosis cases which improved without therapy. Therefore, significant amounts of spontaneous release of IL-1 alpha and beta in vitro from alveolar macrophages in sarcoidosis might be considered as an index for the necessity of systemic corticosteroid treatment.

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A 63-year-old woman with a past history of bronchial asthma was admitted to our hospital with a diagnosis of status asthmaticus. Examination revealed a ring-shaped, calcified stone within the trachea immediately below the vocal cords. As the patient complained of increasing difficulty in breathing, emergency tracheotomy was performed in an attempt to save her life, with success.
Bronchial calculus (broncholithiasis) has been occasionally reported, and it is hypothesized that the calculus is mostly caused by intra-bronchial perforation of calcified lymph nodes around the bronchus. Tracheal calculus is a rare disease, and our case is only the third ever reported in Japan. However, perforation of calcified lymph nodes was probably not responsible for this case, which probably resulted from repeated chronic inflammation and fungal infection.

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A 61-year-old male stonecutter was in excellent health until December 1988 when he was admitted to Miyagikenritsu Semine Hospital with an abnormality on chest X-ray film. Chest X-ray film revealed a left anterior mass that was confirmed on chest CT scan and MRI. Biochemical examinations and serum protein electrophoresis demonstrated hypoproteinemia (5.4g/dl) and hypogammaglobulinemia (7.9%, 0.43g/dl). Lymphocyte subset analysis showed OKT4 epitope deficiency (OKT4 0.1% and Leu3a 28.4%), and decrease of CD4/CD8 ratio (0.65). An encapsulated anterior mediastinal mass and the thymus were resected on January 9, 1989, without difficulty. Histology revealed a thymoma with a spindle cell epithelial component. OKT4 epitope deficiency in a patient with Good's syndrome (thymoma with hypogammaglobulinemia) was our diagnosis. There was no change in the patient's serum immunoglobulin level after thymectomy.
Fifteen cases of Good's syndrome have been reported in Japan, but this is the first report of OKT4 epitope deficiency with Good's syndrome in Japan.

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A 51-year-old man with chief complaints of cough, fever, and dyspnea was admitted to our hospital. Based on a home provocation test, transbronchial lung biopsy specimens, and a serum antibody, we diagnosed summer-type hypersensitivity pneumonitis. In 1983 when the patient was 46 years old, thymectomy was performed for thymoma.
Prior to surgery, bronchoalveolar lavage (BAL) was performed. Total cell count and neutrophils had already increased in BALF. Furthermore, the increase in BALF cell neutrophil count was also seen at the time of admission and after the home provocation test. Because an increase of neutrophils in BALF cells was seen not only at onset but before onset, further studies are required to clarify the role of neutrophils and the factors that increase them in hypersensitivity pneumonitis.

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A case of long-term survival of a female patient with complicated diffuse metastatic leptomeningeal carcinomatosis (DMLC) secondary to lung cancer is reported. A 36-year-old woman, hospitalized with a chief complaint of headache and unproductive cough, was diagnosed as having primary lung adenocarcinoma (T₄N₁M₁ oss) and was given systemic chemotherapy. Although progressive deterioration of her headache continued, repeated neurological examination, cerebrospinal fluid (CSF) examination, and cranial CT scans failed to show evidence of metastasis to the central nervous system, and the only finding suggesting CNS involvement was an elevated CEA level in CSF.
Later in the course of her treatment, the patient suddenly lost her vision and subsequently consciousness due to acute increased intracranial pressure, and emergency ventricular drainage was performed for therapeutic and diagnostic purposes. Malignant cells were found in CSF obtained from a ventricular drainage and she was treated successfully by systemic and intrathecal chemotherapeutic agents. She was discharged after a ventriculo-peritoneal shunt operation for hydrocephalus; a double-dome reservoir was used for continuous intrathecal administration of the anticancer drugs, and a shunt filter was located in the tube to prevent the dissemination of cancer cells. In addition to methotrexate and cytosine arabinoside, ACNU and interleukin-2 were administered intrathecally without serious adverse effects, but no apparent therapeutic effects were noted either. She survived over 2 years after DMLC was first diagnosed. At autopsy DMLC secondary to lung adenocarcinoma was confirmed, but no evidence of leukoencephalopathy due to aggressive intrathecal chemotherapy was found.
Current therapy for patients with DMLC and its clinical problems are discussed in relation to our experience in this case.

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