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When a 74-year-old male patient visited our hospital for the treatment of herpes zoster, his computed tomography (CT) revealed a mass in his right breast, axillary lymph node enlargement, and multiple lung nodules. A histological examination of the breast and lymph node biopsies revealed diffuse large B-cell lymphoma (DLBCL) while the bronchial and salivary gland biopsies showed secondary amyloidosis and Sjögren's syndrome (SjS). According to the Ann Arbor staging, the clinical stage of the lymphoma was evaluated as IIE. The patient achieved a complete remission after six cycles of rituximab, pirarubicin, cyclophosphamide, vincristine, and prednisolone (R-THP-COP) combined with intrathecal chemotherapy to prevent meningeal infiltration and irradiation after chemotherapy. Primary breast lymphoma was diagnosed within 2% of the breast tumor. Only sixteen male cases of breast lymphoma have been previously reported. In those reports, gynecomastia and hormonal therapy accounted for nine cases, but none of the cases coexisted with SjS. The present case is suggestive of the need to investigate possible autoimmune involvement in the development of lymphoma.

Plasma cell leukemia (PCL) is a rare variant of multiple myeloma (MM) with a poor prognosis. Nonsecretory myeloma is also a rare form of MM characterized by the absence of detectable M-protein in the serum and urine. This report describes two cases of nonsecretory PCL. The first patient was an 85-year-old man in whom the lack of monoclonal immunoglobulins made it difficult to make a diagnosis because the malignant cells showed an atypical morphology. He died of rapid disease progression before starting chemotherapy. The second patient was a 78-year-old woman whose tumor cells displayed a typical plasma cell morphology. She was successfully treated with bortezomib-containing chemotherapy.

A 48-year-old man with dyspnea, cough, and fever was found to have a diffuse ground-glass pulmonary lesion without lymphadenopathy on chest X-ray. The lesion shifted to the peripheral lung zones 2 months later when transbronchial biopsy demonstrated noncaseating granulomas with Langhans type giant cells. After 6 more months, prominent bilateral hilar lymphadenopathy and highly elevated serum angiotensin-converting enzyme confirmed the diagnosis of pulmonary sarcoidosis. Such a course is quite rare in that it goes the opposite way of the conventional staging system.

A53-year-01d woman who was hypoxemic due to primary lung adenocarcinoma with both pleuritis and pericarditis carcinomatosa was treated with gefitinib，an inhibitor of the epithelial growth factor receptor (EGFR) tyrosine kinase.The tumor seemed to produce mucin because the extremely high serum KL-6 and almost normal Sp-D values on admission.After 3 days of treatment，the patient became asymptomatic and oxygen was discontinued.The response to this drug was remarkable on chest CT findings.Mucin overproduction could offer a candidate marker to determine the patient subset displaying good responseto gefitinib.

BACKGROUND Inactivation of the retinoblastoma (Rb) gene has been documented in various types of cancer, including lung cancer. Alterations of the p53 and ras genes are also common features in the molecular biology of lung carcinoma, and the authors of this article have reported previously on the prognostic significance of both of them. In the present study, the authors evaluated the prognostic significance of the loss of Rb protein expression alone, then performed a combined analysis of Rb protein and ras p21 status (Rb/ras) as well as an analysis of Rb and p53 protein status (Rb/p53) in patients with nonsmall cell lung cancer (NSCLC). METHODS Ninety-one patients with NSCLC underwent potentially curative resection between 1977 and 1988, 65 of whom received postoperative combination chemotherapy. Tumor specimens were analyzed for Rb protein expression by immunohistochemistry. Univariate and multivariate analyses were performed to assess the association between Rb protein expression and survival. RESULTS Nineteen (21%) of the 91 NSCLCs showed negative Rb protein expression. Positive or negative Rb protein expression (Rb+ or Rb-) as an individual factor was not statistically correlated with survival or prognosis in this cohort of NSCLC patients, although a tendency among Rb- patients to do worse was observed. The authors then combined the Rb protein status with previously studied results of ras p21 and p53 protein expression in the same tumor specimens, and compared the prognosis between the individuals with theoretically the best pattern of gene expression in their tumors and those with theoretically the worst pattern of expression, i.e., Rb+/ras- versus Rb-/ras+ and Rb+/p53- versus Rb-/p53+. In patients with adenocarcinoma, those with Rb-/ras+ tumors survived for a significantly shorter period after surgery (13% 5-year survival) than those with Rb+/ras- tumors (82% 5-year survival) (P = 0.01). Similarly, patients with Rb-/p53+ tumors survived for a significantly shorter period (20% 5-year survival) compared with those who had Rb+/p53- tumors (73% 5-year survival) (P = 0.008). Rb/ras status was a significant prognostic factor (P = 0.02 by univariate analysis, P = 0.048 by multivariate analysis), and Rb/p53 status tended to be significant as a prognostic factor (P = 0.04 by univariate analysis, P = 0.08 by multivariate analysis). In patients with squamous cell carcinoma, neither Rb/ras nor Rb/p53 status was a significant prognostic factor in this cohort. CONCLUSIONS These results suggest that combined immunohistochemical analyses of Rb and ras p21 proteins and of Rb and p53 proteins may indicate their potentially synergistic effects on survival and prognosis. These analyses may also be useful for stratifying patients with adenocarcinoma of the lung into different prognostic groups and identifying populations with different risks of recurrence. Larger prospective studies with Stage I NSCLC patients are necessary to confirm the current findings. Cancer 1997; 79:1329-37. © 1997 American Cancer Society.

Background. Alterations of the p53 gene are one of the most common genetic changes in various types of cancer, including lung cancer. Abnormalities in the ras genes, including point mutations and overexpression, are another common feature in the molecular biology of lung cancer and are associated with a poorer prognosis. The authors' purpose was to determine expression of the mutated p53 gene in nonsmall cell lung cancer (NSCLC) specimens that were studied for expression of ras p21 and to document whether altered p53 expression was also an important factor for survival. Methods. Ninety-six patients with NSCLC underwent surgical resection between 1977 and 1985, 63 of whom received postoperative combination chemotherapy. None received radiation therapy. Tumor specimens were analyzed for altered p53 expression by immunohistochemistry. Univariate and multivariate analyses were performed to assess the association between p53 expression and survival. Results. Fifty-six (58%) of 96 tumor specimens showed altered p53 expression, and 91 patients were analyzed for survival. Altered p53 expression did not correlate with clinicopathologic characteristics except for postsurgical pathologic tumor (pT) classification. The patients with altered p53 expression survived for a significantly shorter period after surgery than those without p53 expression, including all patients who underwent resection and potentially curative resection (P = 0.02 and P = 0.048, respectively, generalized [Wilcoxon test]. Multivariate analysis showed independent prognostic significance for altered p53 expression (hazard ratio [HR] = 1.72, P = 0.04) and surgical cure (HR = 4.69, P < 0.001). The combined analysis of mutated p53 and ras p21 expression in the same tumor specimens revealed that patients with p53- and ras p21-negative tumors survived the longest among those with different p53 and ras p21 features (P = 0.005, generalized Wilcoxon test). Conclusion. Altered p53 expression is a significant and independent negative prognostic factor for patients with surgically resected NSCLC. Combined immunohistochemical analysis of mutated p53 and ras p21 expression can divide patients with NSCLC into more accurate prognostic groups. If the current findings can be confirmed in larger prospective studies, combined immunohistochemical analysis of mutated p53 and ras p21 expression can be a useful clinical tool for stratifying patients with NSCLC into accurate prognostic groups and for identifying the population with a different risk of recurrence.

Among the most common mutations in human lung cancer are those affecting the p53 gene. The expression of p53 in the nucleus is considered an immunohistochemical reflection of the nuclear accumulation of mutant p53 protein, which is coded by the p53 gene with missense mutation and has a prolonged half-life. In the present study, p53 expression detected by means of immunohistochemistry occurred frequently in human lung cancer and was associated with histologic subtypes. The alteration in the p53 gene was found to be a relatively early genetic event in the development and progression of lung cancer and to be maintained in the process of metastasis: abnormal p53 expression was found in both the early and late clinical stages, and identical p53 expression was detected consistently among primary and metastatic lesions from the same patients. Furthermore, an observed association between abnormal p53 expression and the patients' smoking history suggests that the p53 gene could be a common target of tobacco-associated carcinogenesis in lung cancer.

切除肺癌の核DNA量を測定し, また, ras癌遺伝子産物p21蛋白の発現を免疫組織化学的に調べ, それらの肺癌患者の予後における意義を検討した.DNA量を測定した84腫瘍のうち, 19例 (23%) がDNA diploid腫瘍であり, 65例 (77%) がaneuploid腫瘍であった.rasp21の染色性をみた91例のうち, 58例 (64%) が陽性 (weak+strong腫瘍) であった.DNAdiploid腫瘍患者の5年生存率は61%, aneuploid腫瘍患者は35%であり, aneuploid腫瘍患者の予後は有意に不良であった (p

Isolates of M. tuberculosis were analyzed for their DNA fingerprints to facilitate understanding of ongoing transmission of tuberculosis in Sapporo (population 1.87 million), Japan, where the incidence rate of tuberculosis was 15.0 per 100,000 in 2004.Out of all tuberculosis patients registered in the city from November 1998 to December 2003, isolates from culture-positive respiratory tuberculosis cases for whom written informed consent had been obtained, were analyzed by restriction fragment length polymorphism (RFLP). The study included 345 cases (249 men and 96 women) whose isolates were available for DNA patterns.Using standard IS6110-RFLP typing, cases whose isolates shared identical fingerprints were considered to belong to the same cluster. Proportions of clustered cases were evaluated according to their clinical and socio-economical characteristics.Out of 345 cases, 207 (60.0%) were classified into 59 clusters, and 15% of clustered cases having definite epidemiological links. Multiple logistic regression analysis in men showed that age and infectiousness were significantly related to clustering. The adjusted odds ratios (OR) [95% confidence intervals (CI)] were 0.17 [0.03-0.79] for 30-59 years, 0.15 [0.03-0.69] for 60 years or over and 2.35 [1.17-4.70] for those cases assigned as the highest level of transmission of tuberculosis from the infectiousness index of cases. For women the final model showed the adjusted OR [95% CI] were 0.52 [0.22-1.22] for those with previous history of tuberculosis and 0.33 [0.06-1.85] for diabetics. In male cases with a previous history of tuberculosis, most highly infectious cases were significantly associated with clustering (OR [95% CI], 4.53 [1.16-17.68]).The results suggest that highly infectious male tuberculosis cases with endogenous reactivation have contributed to recent transmission of tuberculosis in the studied area.

To find a new method to predict the result of the egg based Ogawa medium using the Mycobacterium Growth Indicator Tube (MGIT) system and to evaluate the usefulness of a new discharge criterion that uses the new prediction method for smear positive pulmonary tuberculosis patients.We compared mycobacterial growth of sputum specimens weekly between the Mycobacterium Growth Indicator Tube (MGIT) and the egg based Ogawa solid media, using a total of 3952 sputum specimens of patients with pulmonary tuberculosis (TB) who underwent chemotherapy in our hospital from September 2001 to March 2006 to find relationship between the results of the two culture methods and to utilize the findings to new discharge criteria of pulmonary TB patients. And we compared the duration of hospitalization between two patients' group: one group using the new discharge criterion, the other the old one.We found that if a specimen shows negative culture on the MGIT system within the first two weeks, the same specimen shows negative or scant growth on the Ogawa media in the 8th week. Introducing this fact as a part of new criteria for hospital discharge of patients with pulmonary tuberculosis, the median duration of hospitalization in our hospital was shortened from 121 days to 71 days and no patient showed treatment failure.We have used the result of sputum culture on Ogawa medium as a standard when we judge infectivity of patients with pulmonary tuberculosis in Japan, but it was one of the reasons why Japanese pulmonary tuberculosis patients stay long in TB hospital. Using our finding, we can predict the results of Ogawa system six weeks earlier, when a specimen shows negative culture on the MGIT system in the first 2 weeks. After we introduced this fact into new criteria for hospital discharge of patients with pulmonary tuberculosis, the median duration of hospitalization in our hospital was shortened and no patient shows treatment failure until now. We highly recommend the usefulness of the MGIT system (especially when a specimen shows negative growth in the first two weeks) as a reliable method of predicting infectivity of patients with pulmonary tuberculosis and propose that the new TB discharge criterion should be widely confirmed and used in other hospitals.

肺内結核腫は結核性胸膜炎の治療開始2～4カ月後に, 稀に出現する肺内結節状陰影である. いわゆる初期悪化の1種で抗結核剤を継続すると次第に縮小する. 肺CTでは胸膜病変と, それに連続した肺内病変がみられ, 内部に低吸収域を認めることが多い. 今回経過を観察しえた2症例で病変は胸膜から始まって次第に肺内へと進展した. 発生機序として肺内の微小病変からの初期悪化とする説があるが, それとは異なる機序が推察された.

We propose (-deltaG(rs)/deltat)/G(rs) obtained from Astograph as an index of dynamic property of the airway. G(rs) represents respiratory conductance. Fluid mechanics suggests that (- deltaG(aw)/deltat)/G(aw) is related to a coefficient of airway contraction or dilatation. G(aw) represents airway conductance. R(rs) (=1/G(rs)) is approximately equal to R(aw) (=1/G(aw)) + Constant. R(rs) and R(aw) represent respiratory and airway resistance, respectively. As R(rs) is thought to be closely correlated to R(aw), G(rs) should be correlated to G(aw). Thus, if G(rs) is used as a substitute for G(aw), (-deltaG(rs)/deltat)/G(rs) should also be related to a coefficient of airway contraction or dilatation. We found that asthmatics had significantly higher (-deltaG(rs)/deltat)/G(rs) than normal subjects. That is, the airway smooth muscles of the asthmatics are more contractive than those of normal subjects.

To explore the mechanism by which lung cancers excessively arise from pneumoconiosis, we determined the altered expression of p53 and Bcl-2 by immunohistochemistry (IHC) in lung cancers, dysplasias and non-cancerous pulmonary epithelia in pneumoconiotics in comparison with those from non-pneumoconiotic patients. We examined p53 expression in squamous cell carcinomas (SCCs) and dysplasias separately in the central and peripheral zones of bronchial trees, based on observations that SCCs from pneumoconiotic patients occurr more frequently in peripheral epithelia than those from non-pneumoconiotic patients (55 of 72 SCCs with pneumoconiosis vs. 33 of 72 SCCs without pneumoconiosis). Forty-one of 72 patients with pneumoconiosis-related lung cancers had altered p53 expression, which was comparable to the positivity of p53 expression in lung cancers without pneumoconiosis. p53 expression was observed significantly more frequently in bronchiolar dysplasias with pneumoconiosis than in those from non-pneumoconiotic patients (13 of 23 vs. 4 of 22), while p53 expression was found in bronchial dysplasias with pneumoconiosis as frequently as those without pneumoconiosis. Moreover, in patients with pneumoconiosis, bronchiolar dysplasias exhibited p53 expression more frequently than bronchial dysplasias (13 of 23 vs. 4 of 19). When comparison was restricted to bronchiolar dysplasias from patients without lung cancer, p53 expression had a strikingly higher frequency in the dysplasias with pneumoconiosis than in those from non-pneumoconiotic patients (8 of 15 vs. 0 of 14). Bcl-2 occasionally was expressed in squamous metaplasias and basal cell hyperplasias, in contrast to p53, for which immunostaining was negative in these lesions. Altogether, our results show that pre-cancerous and/or cancerous targets in pneumoconiosis may be distributed over a more peripheral zone than those in patients without pneumoconiosis. Int. J. Cancer 75:504–511, 1998.© 1998 Wiley-Liss, Inc.

Malignant neoplasms possess multiple genetic abnormalities. Among those, p53 gene abnormalities are the most frequent in human neoplasms. To screen for p53 abnormalities, both immunohistochemistry (IHC) and the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) methods are commonly used, but neither can detect all kinds of p53 abnormalities. In this study, by examining 35 lung cancer specimens simultaneously by the two methods, 12 abnormal cases (34%) were detected by IHC and 9 abnormal cases (26%) were detected by PCR-SSCP. Six abnormal (17%) and 20 normal (57%) cases showed concordant results between the methods, although 9 cases (26%) showed discordance, including 6 IHC-positive cases (17%) and 3 SSCP-positive cases (9%). Because it is known that some p53 abnormalities are detected only by IHC or only by PCR-SSCP, discordant cases should be assessed as possessing abnormalities. Fifteen cases (43%) were finally assessed as abnormal. These results suggest that the two methods together can increase the sensitivity of screening for p53 abnormalities.