[Chronic and acute hypersensitivity pneumonitis in a dairy farmer and his son].

We encountered a dairy farmer and his son with farmer's lung who had worked on the same farm for 25 years and 5 years, respectively. The son was admitted to our hospital because of cough, sputum, and shortness of breath. Chest computed tomography (CT) on admission revealed diffuse ground-glass opacities in both lung fields. Following admission, the clinical symptoms and radiological findings improved spontaneously without specific treatment. A provocation test (following return to work on the farm) elicited recurrence of the symptoms and radiological findings. He was diagnosed with acute hypersensitivity pneumonitis (HP) based on the clinical findings. After quitting his job, no reccurence was noted. The farther was admitted to our hospital complaining of repeated episodes of cough and high fever. He had been diagnosed with lung fibrosis 10 years previously. Chest CT on admission revealed progression of thin-walled cystic changes over ten years. Following admission, his symptoms improved without medication. However, because he has continued working on the farm, his radiological findings have gradually deteriorated. He was diagnosed with chronic HP based on his clinical features. These cases are suggestive of farmer's lung with familial occurrence, difference between acute HP and chronic HP, and long-term prognosis.

[Autopsy case of von Recklinghausen's disease associated with lung cancer, gastrointestinal stromal tumor of the stomach, and duodenal carcinoid tumor].

A 58-year-old man with von Recklinghausen's disease was admitted for further investigation of right chest pain. Chest X-ray revealed multiple emphysematous bullae in both lungs and a tumor shadow in the right upper lobe. Bronchofiberscopy was performed, but an adequate specimen was not obtained. The tumor was diagnosed as a non-small-cell lung cancer with direct invasion to the adjacent rib. Although chemotherapy and radiotherapy resulted in decrease in tumor size, the tumor subsequently increased in size and the patient died 14 months after the first admission. Autopsy revealed multiple emphysematous bullae, poorly differentiated adenosquamous cell carcinoma of the lung, gastrointestinal stromal tumor of the stomach, and duodenal carcinoid tumor. This case suggests the possibility that von Recklinghausen's disease associated with emphysematous bullae is a risk factor for lung cancer. It has also been suggested that the genetic abnormality responsible for von Recklinghausen's disease increases the risk for various types of malignancy. Although von Recklinghausen's disease is reportedly associated with various malignant tumors, it is quite rare for von Recklinghausen's disease to be associated with triple non-neurogenic tumors. Careful observation is mandatory for patients with von Recklinghausen's disease.

Scoring system for differential diagnosis of malignant mesothelioma and reactive mesothelial cells on cytology specimens.

Cytology is the only useful tool in the detection of malignant mesothelioma (MM) at an early stage. No other methods, such as immunocytochemistry or electron microscopy, are available to distinguish MM from reactive mesothelial cells (RMC). Some objective analysis of cytology specimens is necessary. On the basis of our case review and cytological features described in previous articles, we developed a scoring system for malignant mesothelioma (SSMM) of effusion cytology to distinguish MM cells from RMC. Mesothelioma cells in effusions from 22 patients (20 pleural and 2 peritoneal mesotheliomas) were compared with RMC from 20 patients without obvious tumor cells and 50 effusions containing metastatic carcinoma cells. The SSMM is based on characteristic features of mesothelial and malignant cells. The total achievable score is 10 points: one point each is given for variety of cell size, cyanophilic cytoplasm with villosity/windows/bleb, sheet-like arrangement, mirror-ball-like cell clusters, nuclear atypia, and cannibalism, respectively. Further two points each are ascribed for acidophilic large nucleoli and multinucleated cells with more than eight nuclei. The total score for each of the 22 mesotheliomas was more than 5 points. On the other hand, all RMC and the 50 metastatic carcinoma cases scored less than 3 points, aside from two cases that were treated with OK432. No single characteristic feature was observed to be consistent within the 22 mesotheliomas analyzed. Ancillary use of immunocytochemistry, such as podoplanin (D2-40) and calretinin, supported the diagnostic accuracy of the SSMM. SSMM is useful for the differential diagnosis of MM.

[A case of pulmonary MALT lymphoma with 6-year natural history].

A 58-year-old asymptomatic man was referred for investigation of an abnormal shadow on chest X-ray films. Chest computed tomography (CT) revealed an infiltrative shadow containing an air-bronchogram. Video-assisted thoracic surgery was performed for a lung biopsy of an abnormal region in the right upper lobe of the lung. Based on immunohistochemical examinations and gene analysis, the abnormal shadow was diagnosed as primary pulmonary B-cell lymphoma of mucosa-associated lymphoid tissue, t(11; 18)/API2-MALT1. Rituximab-CHOP therapy yieled a complete response. He had abnormal shadows on chest X-ray films in both lung fields since 6 years previously. Retrospective examination of chest radiographs revealed slow growth during the 6 years.

[The improvement of the enforcement rate of the standard regimen (A) of tuberculosis chemotherapy by the introduction of common database system for tuberculosis].

OBJECTIVE: The purpose of this study was to improve the enforcement rate of the standard regimen (A) of tuberculosis chemotherapy. SUBJECTIVE AND METHODS: We introduced the common database system for tuberculosis in three national hospitals in Hokkaido. From January 2002 to December 2003, we collected the anonymous informations of the patients with tuberculosis at the start of treatment, at the discharge and at the end of treatment. Then, we reported the enforcement rate of the standard regimen (A) as a clinical indicator periodically to three hospitals. RESULTS: Four hundred and twenty-nine patients were registered. In patients below 80 years old, the enforcement rate of the standard regimen (A) was 48.5% in 2002. The enforcement rate rose significantly to 62.7% (p = 0.0126) in 2003. In elder smear-positive patients (> or =75) and in elder smear-negative patients (> or =70), the enforcement rate was low (29.1% and 25.0%, respectively). Furthermore in young smear-negative patients (< or =29), the enforcement rate was low (28.0%). As the extent of their disease was minimal, they were treated with other regimens. In patients treated with the standard regimen (A), there were no significant differences in the frequency of adverse effects between elder patients ( 70) and other patients (< or =69). There were also no significant differences in the frequency of changing the regimen between them. Median admission period of 2002 was 114 days. In 2003, it was shortened significantly to 110 days (p = 0.0487). CONCLUSION: By the introduction of the common database system for tuberculosis, the enforcement rate of the standard regimen (A) was improved. Low enforcement rate in young smear-negative patients in an important problem to be improved in the future. The clinical indicator based on the common database system between hospitals, is useful to clarify the problems, and then to improve the quality of medical performance.

Intracellular conversion of irinotecan to its active form, SN-38, by native carboxylesterase in human non-small cell lung cancer.

The anticancer agent irinotecan (CPT-11) is a prodrug converted to its active form, SN-38, by human carboxylesterase (hCE) and the SN-38 is further metabolized to its inactive form, SN-38G. We investigated the expression of hCE in human lung cancer cells as well as the ability of these cells to convert CPT-11 to SN-38 using surgically resected tumor samples and cultured cell lines. SN-38 was 40- to 3,000-fold more toxic to lung cancer cell lines than CPT-11, which acted more time-dependently than SN-38. Although human lung cancer cells expressed hCE in the cytoplasm, hCE expression levels in cancer cells were not correlated with their drug sensitivities. Although intracellular CPT-11 and SN-38 levels continuously increased within 60 min of CPT-11 exposure, SN-38 levels in cells exposed to SN-38 decreased. Cells with the ability to metabolize SN-38 to SN-38G were more resistant to extracellular SN-38 than cells lacking the ability. Of 25 squamous cell carcinomas, 15 were strongly positive for hCE and six were negative. Of 25 adenocarcinomas, four were strongly positive for hCE and 16 were positive, while five were negative. Thus, 70% of non-small cell lung cancers expressed hCE. From these results, we conclude that human lung cancer cells expressed the enzyme which can convert CPT-11 to SN-38 and that intracellular SN-38 converted from CPT-11 may act as a chemotherapeutic agent together with SN-38 absorbed from the outside and augment the dose intensity of SN-38. Therefore, to assess the effects of CPT-11 prior to chemotherapy, it is important to check if lung cancer cells express hCE.