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application/pdf, Objectives The purpose of this study is to examine clinical and pathological features, treatment modality approaches in the elderly, especially in patients aged 80 years and older. Methods From the databases at two educational hospitals during the period from January 1978 and December 2007, medical records of lung cancer patients were retrospectively reviewed. The patient population was divided into three age groups: less than 70 years (the

Paraneoplastic nephrotic syndrome has been reported in various malignancies: malignant lymphoma, colon cancer, lung cancer, and prostate cancer. Of these, lung cancer is the most commonly associated with the syndrome. Here, we report 4 cases of nephrotic syndrome associated with lung cancer, in one of which urinary protein and edema were improved by steroid therapy. These results suggest that in patients with paraneoplastic nephrotic syndrome histologically diagnosed as having minimal change disease (MCD), it is important not only to treat the cancer itself but also to use steroids as early as possible. On the other hand, our results also showed that treatment is still difficult for locally advanced or metastatic tumors. Therefore, when we encounter patients with nephrotic syndrome, it is important to be aware of the association of nephrotic syndrome and lung cancer.

A 74-year-old woman with rheumatoid arthritis was referred for a mass incidentally noted on chest radiograph. Chest CT scan showed cystic lesions in the right lower lobe. The lesion was evaluated as bronchiectasis, and she was followed up. Three years after the initial presentation, the appearance of the lesion had changed significantly and an elevated air-fluid level in the cystic structures was shown on chest CT scan. The preoperative serum progastrin-releasing peptide (proGRP) level was elevated (108.0 pg/ml; normal

Hypersensitivity pneumonitis (HP) is mediated by a Th1 immune response. Transcription factor GATA binding protein-3 (GATA-3) is believed to be a key regulator of Th2 differentiation and thus might play regulatory roles in the pathogenesis of hypersensitivity pneumonitis (HP).We examined the effect of GATA-3 overexpression on the development of HP in mice.Wild-type C57BL/6 mice and GATA-3-overexpressing mice of the same background were used in this study. HP was induced by repeated exposure to Saccharopolyspora rectivirgula, the causative antigen of farmer's lung.Antigen exposure resulted in a marked inflammatory response with enhanced pulmonary expression of T-bet and the Th1 cytokine interferon (IFN)-gamma in wild-type mice. The degree of pulmonary inflammation was much less severe in GATA-3-overexpressing mice. The induction of T-bet and IFN-gamma genes was suppressed, but a significant induction of Th2 cytokines, including IL-5 and IL-13, was observed in the lungs of GATA-3-overexpressing mice after antigen exposure. Supplementation with recombinant IFN-gamma enhanced lung inflammatory responses in GATA-3-overexpressing mice to the level of wild-type mice. Because antigen-induced IFN-gamma production predominantly occurred in CD4+ T cells, nude mice were transferred with CD4+ T cells from either wild-type or GATA-3-overexpressing mice and subsequently exposed to antigen. Lung inflammatory responses were significantly lower in nude mice transferred with CD4+ T cells from GATA-3-overexpressing mice than in those with wild-type CD4+ T cells, with a reduction of lung IFN-gamma level.These results indicate that overexpression of GATA-3 attenuates the development of HP by correcting the Th1-polarizing condition.

CA19‐9 is a specific tumor marker in patients with gastrointestinal cancer; however, some patients with respiratory disease can have elevated serum levels of CA19‐9 as well. In this study we evaluated serum CA19‐9 levels of patients with nonmalignant respiratory diseases. We also estimated the prognostic significance of elevated serum levels of CA19‐9 in patients with interstitial lung diseases. The study included 554 patients who had been diagnosed at our hospital during the period of 1984–2005. Serum CA19‐9 levels in these patients were measured with a commercially available kit. Elevated levels (>37 U/mL) of CA19‐9 were observed in 30.7% of patients with lung cancer. Furthermore, 38.9% of patients with idiopathic interstitial pneumonia (IIP), collagen disease‐associated pulmonary fibrosis (CDPF), diffuse panbronchiolitis (DPB), and bronchiectasis had elevated serum CA19‐9 levels. Survival rates were significantly lower in patients with interstitial lung diseases (IIP and CDPF) and elevated serum CA19‐9 levels than in those with levels in the normal range (P=0.0065). Serum CA19‐9 was elevated in some patients with nonmalignant diffuse lung diseases. Therefore, clinicians should pay attention to the evidence that increased serum CA19‐9 levels can be found in nonmalignant respiratory disease patients. In patients with IIP and CDPF, elevated serum CA19‐9 levels may be related to poor prognosis. J. Clin. Lab. Anal. 21:103–106, 2007. © 2007 Wiley‐Liss, Inc.

We report on an obese man with sleep stage-dependent apnea. His type of apnea was predominantly central during non-rapid eye movement (NREM) sleep, while it was obstructive during rapid eye movement (REM) sleep. We found significantly more and more severe apneas during REM sleep compared to NREM sleep. His apneas were remarkably reduced by position adjustment, suggesting that upper airway collapse played a key role in the induction of both types of apnea. As his apneic patterns were dependent on the sleep stages, we assumed that the balance between upper airway obstruction and instability of central respiratory control might be important in determining the expression types.

A 37-year-old man was referred to our hospital with complaints of dyspnea and general fatigue. Chest radiograph and CT scan revealed thickness of bronchovascular bundles in both lungs. In spite of various examinations, the primary lesion was not identified. He received chemotherapy containing TS-1 and cisplatin. Pulmonary lymphangitic carcinomatosis disappeared and the patient achieved a good partial response. He survived for 14 months after the chemotherapy. We believe the combination of TS-1 and cisplatin is one of the attractive options for patients with cancer of unknown primary site.

OBJECTIVES: To assess the frequency of fever and pneumonia after fiberoptic bronchoscopy (FOB) in older people and to evaluate increased risk for these two adverse events with increasing age. DESIGN: Prospective study. SETTING: University hospital system. PARTICIPANTS: Three hundred fifty-eight patients, with 165 (46.1%) patients aged 70 and older, undergoing bronchoscopy. MEASUREMENTS: Indications, abnormal bronchoscopic findings, sampling procedures, final diagnosis, and fever and pneumonia after bronchoscopy. RESULTS: With regard to the indication for bronchoscopy and abnormal bronchoscopic findings, there was no statistical difference between elderly patients (≥70) and younger patients (

In vivo effect of a bolus combination with 5-fluorouracil (5-FU) and CPT-11 was studied against experimental rat lung cancer, SLC cells. 5-FU and CPT-11, when administrated individually, showed dose-dependent inhibition against the tumor (ID50, 7.0 mg/kg/day and 16.0 mg/kg/day, respectively). 5-FU synergistically enhanced the sensitivity of the tumor cells to CPT-11 and permitted the administration of approximately a one-third lower dose of CPT-11 to obtain the same inhibition against the tumor cell growth. The ID50 of CPT-11 alone (16.0 mg/kg/day) was reduced to 4.8 mg/kg/day when combined with 5-FU at 2.5 mg/kg. There were no deaths caused by toxicity in the combination group, and for lower doses (less than 4 mg/kg/day) of CPT-11 combined with 2.5 mg/kg/day of 5-FU, all rats showed less than 10% body weight loss at the end of the experiments. When the tumor weights were evaluated by using isoeffect plot analysis, the data points resulting from the combination showed a synergistic interaction between these agents. There was no significant increase of toxicity as assessed by the body weight. The results might support for the use of the combination of 5-FU and CPT-11 in cancer chemotherapy.

SummaryPulmonary large-cell neuroendocrine carcinoma (LCNEC) has been characterized by highly aggressive behavior, with early spread to both regional lymph nodes and distant sites and a rapidly fatal course. In fact, no reports have described an advanced pulmonary LCNEC patient who has had long-term survival. A patient with large-sized pulmonary LCNEC, who is free of disease 11 years after surgery and postoperative chemotherapy, was reported.

Summary Spontaneous regression is partial or complete reduction of a malignant tumor without treatment or in the presence of therapy that is considered inadequate to exert a significant influence on neoplastic disease. We report herein a patient with lung cancer who had a spontaneous regression of scalp metastasis with no treatment performed. This is the first report of the spontaneous regression of scalp metastasis of lung cancer. The patient should be carefully followed up to chart his unusual clinical course.

Summary Pulmonary lymphangioleiomyomatosis (PLAM) is a rare disease, which occurs mainly in women of reproductive age, and occasionally in postmenopausal women. We report a small pulmonary metastatic uterine body cancer in a 63-year-old female patient with PLAM. In patients with PLAM, differential diagnostic consideration is proliferation of pneumocytes and PLAM cells in addition to benign tumor as well as primary and metastatic lung cancer. We emphasize difficulties in the clinical and roentgenological diagnosis in this kind of combined pathology. Even if the association we describe is probably fortuitous, not only a primary but also a metastatic tumor is suspected when a solitary pulmonary nodule is detected in a patient that has been previously treated for carcinoma in any organs.

Summary Thrombocytopenia is one of the most important and serious co-morbid conditions in patients with hematological malignancies as well as non-hematological solid tumors. We report herein a small cell lung cancer (SCLC) patient with idiopathic thrombocytopenic purpura (ITP) who was successfully treated with chemotherapy containing cisplatin and etoposide. It is probably safe to administer chemotherapeutic agents for some cancer patients with ITP, but prevention or minimization of toxicities of these chemotherapeutic agents is very important. Full consideration about the indication of chemotherapy and careful observation are required for such patients.

To evaluate the relationship between serum levels of sialyl Lewis X-i antigen and lung metastasis in patients with non-small cell lung cancer (NSCLC), we measured the serum level of the antigen in 299 patients with untreated locally advanced or metastatic NSCLC. Before treatment, serum levels of sialyl Lewis X-i antigen were significantly higher in patients with lung metastasis than in those without lung metastatis (p = 0.0001). Of 201 patients without lung metastasis at the time of primary diagnosis, 121 patients died between July 1987 and December 1995. Serum levels of sialyl Lewis X-i antigen in 21 patients who developed lung metastasis during the period were significantly higher than those in 100 patients who did not develop lung metastasis (p = 0.0171). Our results suggested that sialyl Lewis X-i antigen might be a good indicator for the presence or development of lung metastasis, and it might provide clinical information about the management of patients with NSCLC.

Urokinase-type plasminogen activator (u-PA) is known to be secreted by malignant cells during proliferation and migration, and is associated with tumour cell invasion and metastasis. This study was undertaken to evaluate whether u-PA is significantly increased in carcinomatous pleural fluids compared to those due to other aetiologies, and to identify the cells in the pleural space that are involved in its accumulation. Using an enzyme-linked immunosorbent assay, we quantified u-PA in the pleural fluid specimens of 40 patients with carcinomatous pleuritis, 18 with tuberculosis, 18 with parapneumonic pleuritis and 11 with congestive heart failure (CHF). The level of u-PA was elevated in carcinomatous pleural fluid compared with the level in transudative pleural fluid from patients with CHF (p

Cytokeratins form part of the cytoskeleton of both normal and malignant epithelium. A novel tumor marker measuring cytokeratin 19 (CK-19) fragment has been introduced and proven to be suitable for monitoring therapy and following cases of non-small cell lung cancer, squamous cell lung cancer in particular. However, whether the serum level of CK-19 fragment reflects the number of proliferating tumor mass remains unknown. We studied the CK-19 fragment produced by two human squamous cell lung cancer cell lines. In Western blotting analysis, culture supernatants of both cell lines displayed bands of 37 and 40 kDa, which represented the CK-19 fragment and the intact CK-19, respectively. Gel filtration demonstrated that a part of soluble CK-19 was released as a large complex form in culture supernatants. The level of CK-19 fragment in culture supernatants increased during the exponential growth phase. CK-19 level decreased by an addition of a cytotoxic agent to non-significant level though the transient release of CK-19 fragment occurred during the first 2 days. After all, soluble CK-19 fragments were detected in culture supernatants of human lung cancer cell lines and its level reflected proliferating cancer cells though it was not determined whether CK-19 fragments were released directly from live cells.

茨城県における肺癌診療の現状, 特に検診の関与の把握を目的として筑波大呼吸器内科および関連8医療施設で診断された未治療原発性肺癌1100例を対象とした臨床的検討を行った.症例を発見動機により検診発見群, 他疾患経過観察中発見群および症状発見群の3群に分け解析した.検診発見群, 症状発見群の割合はそれぞれ15.0, 71.2%であった.検診発見群および症状発見群の中でI期例の占める割合はそれぞれ50.3%, 8.8%であり, 非小細胞癌の切除率はそれぞれ60.3%, 16.8%であった (それぞれp=0.0001).50歳未満の例においても検診発見群の1期例, 切除例の占める割合は症状発見群に比較し有意に高率であった.単, 多変量解析による予後の検討では検診発見群の予後が他の2群に比較して有意に良好であった.検診発見率の向上など今後さらに早期発見, 早期治療をはかることのできる診療体制の確立に努力すべきであると考えられた.

We describe a rare case of a 64-year-old man with left atrial thrombus and stage IB adenocarcinoma of the lung. The patient was successfully treated with simultaneous cardiac operation and lobectomy for lung cancer.

Several monoclonal antibodies specific to the human T-cell receptor (TCR) variable (V) region were used to examine whether T-cell oligoclonality plays a key role in the development of the T-cell-mediated lung disease, summer-type hypersensitivity pneumonitis (SHP). The usage of TCR V-regions was examined using bronchoalveolar lavage (BAL) and matched peripheral blood lymphocytes (PBL) in patients with SHP. In 18 SHP patients, the majority of lymphocytes in both BAL and PBL was CD3+ cells (94.2 vs. 63.9%, respectively), which was similar to that in normals (n = 7). Of CD3+ lymphocytes in a SHP patient, the percentage of CD4+ cells in BAL was reduced compared to those in paired PBL, whereas the percentage of CD8+ cells was significantly elevated. In contrast, the percentage of CD4+ cells was much higher than that of CD8+ cells in both BAL and PBL of normal subjects. While a majority of CD3+ T cells expressed TCR alpha/beta+ in BAL and PBL from both SHP patients and normal controls, a marked increase of the expression of TCR gamma/delta+ was observed in PBL in 4 out of 18 SHP patients. A markedly increased prevalence (> 3 SD) of specific TCR alpha/beta+ V-region families in BAL was detected in 5 of 18 patients with SHP as compared to normal controls, whereas no specific increase was found in PBL. Increased V beta 8 was detected in 3 cases; V beta 6 was observed in 1 patient, and V beta 5 in another patient.(ABSTRACT TRUNCATED AT 250 WORDS)

To examine the relationship between smoking and lung adenocarcinoma in female patients, we performed a retrospective chart review for 470 patients with lung adenocarcinoma at our hospital. The proportions of non-smokers were higher in female patients than those of male patients. A significant difference in smoking history was found between female and male patients. Not only active smoking but also passive smoking may influence the development of female lung adenocarcinoma, which reinforces the need for effective programmes aimed refraining from smoking and cessation among men as well as women.

Lymphocytes obtained by bronchoalveolar lavage (BAL) in hypersensitivity pneumonitis (HP) and pulmonary sarcoidosis (PS) are believed to be derived from interstitial inflammatory lesions of the lung in which lymphocytes have migrated from the blood. Because cellular motility is one of the important factors in lymphocyte migration, we investigated the motility of BAL lymphocytes from 12 patients with HP and 12 with PS, as well as their responsiveness to chemoattractants in vitro by modified Boyden chamber method. Motility was evaluated by the number of migrated cells and the migration distance. The numbers of migrated BAL lymphocytes from patients with HP and PS in albumin-containing medium were 318.3 +/- 93.0 (mean +/- SD) and 207.6 +/- 35.5, respectively, and were greater than those of BAL lymphocytes from normal control subjects (133.3 +/- 40.9) and blood lymphocytes, and comparable with those of mitogen-activated blood lymphocytes. The motility of BAL lymphocytes in these diseases compared with blood lymphocytes was also increased in protein-free medium. In addition, the culture supernatants of alveolar macrophages (AM) enhanced the motility of BAL, mitogen-activated, and blood lymphocytes. These results suggest that BAL lymphocytes in these diseases are functionally motile, and their enhanced motility, as well as mediators from AM, may facilitate the accumulation of lymphocytes at the epithelial surface.

When selecting anti-hypertensives, most physicians do not consider daily blood pressure (BP) variation. To evaluate the effectiveness of anti-hypertensives on the temporal profile of BP, we proposed three new parameters obtained by ambulatory BP monitoring and evaluated these parameters by comparing 5 mg of amlodipine and 40 mg of nifedipine coat-core. Hypobaric values were determined by subtracting BP data collected before administration of the drug from those collected after drug treatment at the corresponding time of day. The hypobaric curve was drawn by plotting the hypobaric values in chronological order, with the time at which the drug was taken set as the starting point. The hypobaric area was the area encircled between the 0 mmHg level line and the hypobaric curve. For amlodipine, the hypobaric areas of systolic blood pressure (SBP) and diastolic blood pressure (DBP) were -19,110 mmHg/min and -10,695 mmHg/min, respectively. Systolic BP decreased -13.3 mmHg, and DBP BP -7.4 mmHg as daily averages. For nifedipine coat-core, the hypobaric areas of SBP and DBP were -32,235 mmHg/min and -18,150 mmHg/min, respectively. Systolic BP decreased -22.3 mmHg and DBP -12.6 mmHg as daily averages. From the hypobaric curves, the trough-to-peak ratios of amlodipine and nifedipine coat-core were measured as 0.67 and 0.60, respectively. The total anti-hypertensive power of nifedipine coat-core, measured by the hypobaric area, was 1.69 times more potent than that of amlodipine. These parameters seem to be useful for evaluating the daily temporal profile of the BP-lowering effects of anti-hypertensive drugs.

Seventeen cases of hypersensitivity pneumonitis (HP) at a symptomatic phase were categorized into two groups based on computed tomographic (CT) findings and histologic features of transbronchial lung biopsy specimens, HP accompanied by lung fibrosis (fibrosis group), and HP unaccompanied by lung fibrosis (nonfibrosis group). The fibrosis group comprised bird fancier's lung and HP of unknown etiology, whereas the nonfibrosis group mainly comprised summer-type HP. Comparison of results of pulmonary function tests between these two groups confirmed a restrictive impairment in the fibrosis group. Analyses of cellular components of bronchoalveolar lavage (BAL) fluids revealed lymphocytes, especially CD8+ T lymphocytes, were significantly increased in the nonfibrosis group in comparison with the fibrosis group, whereas CD4+ T cells were increased to the same level in the both groups. Analyses of the onset of disease showed that acute onset was observed mainly in nonfibrosis group and strongly correlated with increased CD8+ T lymphocytes in BAL fluids, while insidious onset was related to lung fibrosis and relatively increased CD4+ T lymphocytes in BAL fluids. These findings raise the possibility that highly elevated CD8+ T cells might have a protective effect on pulmonary fibrosis or that relatively increased CD4+ T cells might play an important role in the pathogenesis of pulmonary fibrosis of HP at the chronic phase.

There have been few reports on clinical characteristics of lung cancer patients with previous or simultaneous upper aerodigestive cancers. To evaluate them, we conducted a retrospective study. The medical records of all lung cancer patients at our division from January 1984 through July 2008 were reviewed. Twenty-one (1.7%) of 1242 patients had previous or simultaneous upper aerodigestive cancers. Twenty patients were smokers. For non-small cell lung cancer (NSCLC), 6 patients underwent surgical resection and 3 were treated with chemotherapy. Three small cell lung cancer (SCLC) patients had chemotherapy. None of the severe complication related to the comorbidities were observed. The median survival for NSCLC and SCLC patients was 15 and 6 months, respectively. For patients with upper aerodigestive cancers, smoking cessation, a chest radiograph or computed tomography scan at least yearly and swift evaluation of signs or symptoms that are suggestive of lung cancer should be recommended.

Immune complexes formed in the airside may be involved in the early parenchymal changes in hypersensitivity pneumonitis. The present study was undertaken to compare the responses of animals after an intratracheal injection with preformed immune complexes to those of patients with acute hypersensitivity pneumonitis, with special emphasis on sequential bronchoalveolar lavage findings and the possible role of chemotactic factors in the immune complex-induced lung injury. An increased number and percentage of polymorphonuclear cells could be detected in bronchoalveolar lavage fluids of guinea pigs within 48 hr following an intratracheal injection of preformed immune complexes. Chemotactic factor activity preceded the observed increase of polymorphonuclear cells in bronchoalveolar lavage fluids, suggesting a role for chemotactic factors in the sequestration of these cells in the lung. In addition, this study confirmed the usefulness of bronchoalveolar lavage in evaluating the pulmonary findings because the changes in bronchoalveolar lavage cell populations correlated with sequential histological findings. The sequential characteristics of the involved areas were noted to be of a peribronchial or bronchiolar infiltration with polymorphonuclear cells at early stages, then alveolar sac infiltration, followed by mild infiltration of mononuclear cells into the alveolar walls. The findings suggest a possible role for chemotactic factors in the accumulation of polymorphonuclear cells, and the sequential changes of bronchoalveolar lavage and histological findings in animals are comparable to those in patients with acute hypersensitivity pneumonitis.

Serum levels of sialyl SSEA-1 antigen, a carbohydrate antigen, were measured by radioimmunoassay in 142 patients with nonmalignant lung diseases. In 20 of 41 patients with fibrosing lung disease, either idiopathic or associated with collagen disease, the serum sialyl SSEA-1 levels were abnormally elevated. In patients with other lung diseases, the serum levels were almost within normal limits, less than 38.0 units/ml. In fibrosing lung disease the serum levels ranged from 13.8 to 147.0 units/ml and were largely concurrent with the degree of disease activity. The therapeutic effects of corticosteroid, which were evaluated with clinical-radiographic-physiologic scores and survivals in the patients with elevated serum levels, were significantly lower than those of the patients with the normal range of antigen levels. An immunohistochemical study performed on autopsied lungs from five patients with fibrosing lung disease indicated that the antigen was selectively expressed in the pulmonary epithelial cells that covered the remodeling alveolar septi in the lungs. No antigen was detectable by immunostaining in normal pulmonary epithelium among five normal lungs. From these findings, it is thought that the elevated levels of serum sialyl SSEA-1 may be derived from proliferating epithelial cells that were dominant in the late stage of fibrosing lung disorders. The measurements of serum sialyl SSEA-1 in patients with fibrosing lung disease may be clinically useful in establishing the degree of disease activity that has an influence on patient prognosis and therapeutic response.

We defined optimal conditions for detection of cryptococcal antigen using latex particles sensitized with anti-C. neoformans globulin fractionated by 40 % saturated ammonium sulfate. Latex particles, with a diameter of 0.81 μm, were sensitized with 20 μg of anti-C. neoformans globulin per mg latex. The agglutination test was performed using a mixture of 75 μl of protease treated serum or cerebrospinal fluid (CSF) and 25 μl of sensitized latex suspension. After 10 minutes reaction on a rotator, the agglutination was read. We compared the minimal concentration of polysaccharide antigen detectable with our materials and procedure and with commercially available kits and obtained almost the same sensitivities. However, our procedure was also capable of detecting antigen in soluble immune complexes in patient's serum. The sensitivity of our latex agglutination test using the sensitized latex particles was found to be 100% in cases of cryptococcal meningitis, 81.8% in pulmonary cryptococcosis and 75 % in cutaneous cryptococcosis. The specificity of our test was 100% with sera and 95% with CSF. We concluded that commercial kit B was the more useful because of its protease pre-treatment which reduced the problems of false positives due to rheumatoid factor and false negatives due to soluble immune complexes.

A 66-year-old man, who was discovered to have human immunodeficiency virus (HIV) infection 22 months previously and was treated with highly active antiretroviral (HAART) therapy, developed giant cell carcinoma of the lung. In English literature, this is the first case of such cell type of lung cancer during HAART therapy. Since giant cell carcinoma of the lung occurs mainly in elderly men who smoke heavily, there may not be a possibility that the HIV or HAART was causative in our patient.

Study objectives There have been few reports on clinical characteristics of lung cancer patients with previous or simultaneous urologic cancers. Additionally, it was scarcely reported whether these patients could tolerate standard therapy. To evaluate them, we conducted a retrospective study. Methods The records of patients with lung cancer who had previously or simultaneously urological cancers seen in our division between January 1985 and August 2007 were reviewed. Results During the study period, 1,105 patients with lung cancer were seen at our division. Thirteen (1.2%) had previous or simultaneous urological cancers (11 males). Eleven patients were smokers. The diagnosis of urological cancers preceded the diagnosis of lung cancer in all but three patients, for whom the diagnosis of urologic cancers was made during the workup of primary lung cancer. Histologically, the lung cancers included six squamous cell carcinomas, four adenocarcinomas, and three small cell lung cancers. Four underwent surgical resection. Six were treated with platinum-containing chemotherapy, but none of them developed severe renal toxicity. The median survival following the diagnosis of lung carcinoma for NSCLC patients was 18 months, and for SCLC it was 24 months. The cause of death in the 12 patients who died in the study period was directly related to lung cancer, and recurrence of urological cancers was observed in none of the patients. Conclusions For patients with urological cancers, smoking cessation, a chest radiograph or CT scan at least yearly and swift evaluation of signs or symptoms that are suggestive of lung cancer should be recommended.

Gefitinib is a selective epidermal growth factor receptor tyrosine kinase inhibitor, which blocks signal transduction pathways implicated in proliferation and survival of cancer cells. Long-term survival in patients with metastatic non-small-cell lung carcinoma (NSCLC) treated with gefitinib has recently been reported. We showed herein two cases of fatal rapid recurrence after a long-term disease control by gefitinib. The biology of fatal aggressive recurrence of gefitinib-treated NSCLC is not well characterized. Regardless of the mechanism, however, physicians treating patients with gefitinib should be alert to the possibility of fatal rapid recurrence after a long-term disease control by this drug.

Chemotherapy is considered to have a marginal impact on survival. The purpose of this study was to evaluate the rate of long-term survival in patients treated with chemotherapy for advanced non-small cell lung cancer (NSCLC).The case records of 109 patients with NSCLC treated with chemotherapy from March 1998 to March 2007 were reviewed.Fourteen (12.8%) and seven (6.4%) patients survived for more than two or three years, respectively. All of the 14 patients had performance status (PS) 0 or 1, and they were given a platinum-containing chemotherapy as initial treatment. By means of univariate analysis, good PS and gefitinib therapy were proved to be good prognostic factors. With Cox's model analysis, these two variables were confirmed as significant determinants of survival.A small but definite proportion of patients with locally-advanced and metastatic NSCLC might potentially survive for more than 2 years with appropriate chemotherapy.

Study Objectives Squamous cell carcinoma antigen (SCC) has been found in elevated amounts in patients with squamous cell lung cancer (SQLC). Elevated levels have also been found among patients with nonsquamous cell lung cancer (NSQLC) and in subjects with nonmalignant pulmonary disease (NMPD). The purpose of the current study was to evaluate SCC levels among a large number of patients with SQLC, NSQLC, and NMPD. Six hundred thirty-nine lung cancer patients, including 201 SQLC patients and 299 patients with NMPD, who were diagnosed at our hospital up to 2006 were entered. Serum SCC levels were measured with a commercially available kit. Results Elevated levels (>1.5 ng/ml) of SCC were observed in 52.7% of SQLC patients, but in only 14.2% of NSQLC patients. There was a statistically significant difference in positive rate between SQLC and NSQLC patients. None of the NSQLC patients had serum SCC levels greater than 40.0 ng/ml. Among subjects with NMPD, 28.4% had elevated levels of SCC. However, none of the NMPD patients had serum SCC levels greater than 20.0 ng/ml. Conclusions Serum levels of SCC can be elevated (

With the rising age, more patients will be diagnosed with one or more other serious illnesses. This study was undertaken to evaluate the frequency of co-morbid illnesses in patients with respiratory diseases, and to compare the frequency between the elderly and the younger patients. We performed chart review of 2764 patients with respiratory disease who admitted in three hospitals in Japan between January 1990 and March 2005. Co-morbid illnesses were observed in 69.5% of 2764 patients with respiratory disease. In 1150 patients 70 years or older, 83.9% of them had co-morbid illnesses. The prevalence of co-morbid illnesses in patients with respiratory disease clearly rose with increasing age (p= 0.0001), the largest increase occurring after the age of 50. Charlson index in patients with respiratory disease clearly rose with increasing age (p= 0.0001). In both elderly (or= 70 years) or younger (70 years) groups of patients, co-morbid illnesses did not influence on the choice of diagnostic procedure. Although the presence of co-morbid illnesses in our patients with non-malignant respiratory disease did not influence on the choice of treatment, however, the presence of co-morbid illnesses in elderly patients with malignant respiratory disease apparently discouraged the choice of standard therapy. Clinical research should address appropriate therapies not only for the elderly patients without co-morbid illness but also for those with co-morbid illnesses. Being aware of the co-morbid illnesses will allow improved management and the planning of appropriate support to a wide range of elderly patients with respiratory disease with important and peculiar needs for care.

Background The proportion of tumor disappearance rate (TDR) on conventional computed tomography (CT) is associated with less aggressive biology, and patients with small peripheral adenocarcinoma accompanied by the TDR component showed better prognosis. These findings led us to the idea that even advanced-stage adenocarcinomas with a higher TDR in the primary lesion on CT might suggest slowly progressing cancer. This study was designed to determine the value of the TDR area in the primary site of advanced-stage lung adenocarcinoma with CT and correlate the CT findings with clinical outcome. Patients and Methods In 103 patients with stage IIIB and IV lung adenocarcinoma, CT appearances and clinical data were reviewed retrospectively. Three methods were used in the evaluation of the TDR area: method I, consolidation on mediastinal windows/mass on lung windows > 75% or not; method II, maximum diameter on mediastinal windows/maximum diameter on lung windows (diameter ratio) > 75% or not; and method III, TDR area on lung windows > 25% or not. Results In univariate analysis, patients with lung adenocarcinoma with TDR have a more favorable prognosis than those without TDR in all 3 methods (method I, P = 0.001; method II, P = 0.024; method III, P = 0.014; log-rank test). In multivariate analysis, a favorable prognosis in patients with adenocarcinoma with TDR was shown in method I ( P = 0.015) and method III ( P = 0.006). Conclusion As shown in patients with small peripheral lung adenocarcinoma, those with TDR on CT tended to have a good prognosis in contrast to those without TDR, even in patients with advanced-stage lung adenocarcinoma. Prospective study to confirm these results will be required.

Utilization of psychotropic drugs including hypnotics, sedatives, and parenteral morphine for terminally ill patients with respiratory disease has not been reported precisely. To better understand these drugs for dying patients with respiratory disease, we focused on the last month of life of them. A chart review, which was focused on symptoms and managements, in the last month of life of 337 patients who died of respiratory disease between April 2000 and March 2005 were performed. Hypnotics were prescribed in 35.8% and 23.2% of patients with malignant and non-malignant disease, respectively. Sedatives such as haloperidol and midazolam were utilized in 34.4% of patients with malignant disease, and 30.4% of those with non-malignant disease. Sixty-seven percent of patients with malignant and 22.4% of those with non-malignant disease had parenteral morphine. In patients with malignant disease, three of the main reasons for administration of morphine were pain, dyspnea, or terminal restlessness. In all of the patients with non-malignant disease, however, parenteral morphine was prescribed for the treatment of dyspnea. Our results showed that psychotropic drugs and parenteral morphine are required in some of terminally ill patients with respiratory disease. Although careful individualization of medication is appropriate, guideline for the prescribing psychotropic drugs for these patients will be required.

Mucosa-associated lymphoid tissue lymphoma (MALToma) has been reported in several organs. Among MALTomas, thymic and pulmonary MALTomas are rare. The present report describes a patient with Sjögren's syndrome who presented thymic and pulmonary MALTomas. Although the exact pathogenetic relationship between these two tumours is uncertain, it is likely that the underlying immune dysregulation related to Sjögren's syndrome contributed to the occurrence and the unusual manifestation of MALTomas in this patient.

Objectives. KL-6 is a specific marker in patients with interstitial lung diseases (ILDs); however, the relationship between elevated levels of KL-6 and subsequent mortality is not well defined. To determine if elevated serum levels of KL-6 are associated with increased mortality, and to identify the most suitable cut-off level of KL-6 by which to distinguish between good prognosis and poor prognosis, we evaluated the prognostic significance of serum KL-6 levels in patients with stable-state ILDs. Methods. Two hundred and nineteen patients diagnosed with ILDs (152 with idiopathic interstitial pneumonia and 67 with collagen disease-associated pulmonary fibrosis) at Tsukuba University Hospital from April 1999 to October 2005 were entered in this study. Serum KL-6 levels in patients with ILDs were measured with a commercially available enzyme immunoassay kit, and these patients were then followed up. Results. During the follow-up period, 58 of the 219 patients died of respiratory failure. Patients who died during this period had higher levels of KL-6 than did those who did not (P = 0.0004). The receiver operating characteristic curve analysis showed 1000 U mL−1 as the most suitable cut-off level by which to distinguish between the two groups of patients. The 95% specificity serum KL-6 level with poor outcome was 2750 U mL−1. In univariate and multivariate analysis, elevated serum KL-6 (>1000 U mL−1) in the stable state indicated poor prognosis (P = 0.0005, log-rank test; P = 0.0001, Cox proportional hazard model). Conclusions. Elevated KL-6 level may provide simple, yet valuable information by which to identify patients with ILDs who are at increased risk for subsequent mortality.

A 71-year-old man who had small cell lung cancer was referred to our institution. Before starting chemotherapy, anemia progressed and stool examination was positive for occult blood. An abdominal computed tomography scan with contrast medium enhancement of the gastrointestinal tract disclosed a small intestinal tumor. Histological examination after the surgery confirmed that the tumor was metastasis of lung cancer. The patient survived for 3 years after the resection. Although clinically apparent metastases of lung cancer to the small intestine are rare and are reported to have a poor prognosis, early detection and intervention might enhance the chance of survival.

We analyzed the T cell receptor (TCR) repertoire of bronchoalveolar lavage fluid (BALF) lymphocytes from polymyositis (PM) and dermatomyositis (DM) patients with interstitial pneumonitis (IP) to elucidate the pathogenic mechanisms of IP in these disorders. Samples from 2 PM patients, 1 DM patient and 3 healthy controls were used. RNA was isolated from BALF, cDNAs were synthesized, and family PCR and Southern blot analysis were performed by primers specific for TCR BV1-25 and TCR BC to determine TCR repertoire. We examined single-strand conformation polymorphism (SSCP) to evaluate T cell clonality. The CDR3 region of TCR BV genes in BALF T cells were determined by DNA sequencer. Our examination showed that TCR repertoire of T cells in BALF was heterogeneous both in patients with PM/DM and control subjects. SSCP analysis demonstrated an increased number of accumulated T cell clones in BALF of three PM/DM patients, but not in the healthy subjects and the junctional sequence analysis showed the presence of conserved amino acid motifs (RGS, GLA, LQG, SGG, DRG, GTS, TSGR, GGS, GQA, GAG, GTG) in the TCR-CDR3 region of BALF lymphocytes from PM/DM patients, which were not detected in the control. Our findings suggest that T cells in BALF may recognize the restricted antigen and accumulate via antigen-driven stimulation, suggesting that T cells may play a crucial role in the development of IP in patients with PM/DM.

Squamous cell carcinoma antigen (SCC) is still a widely used tumor marker for monitoring non-small cell lung cancer (NSCLC), although recent reports discourage its routine use because of low sensitivity. This is a study evaluating the efficacy of SCC and CYFRA21-1 in diagnosing NSCLC. A chart review was performed in a university hospital in Japan, covering a period of 10 years, up to October 2004. During the study period, 142 (35.5%) among 400 NSCLC patients diagnosed, received serum assays of both SCC and CYFRA21-1. Elevated SCC and CYFRA21-1 levels were found in 29.6% and 59.2% of patients, respectively. SCC sensitivity was only 13.0% but CYFRA21-1 sensitivity rose to 73.9% in metastatic patients. The adjunct of SCC increased the CYFRA21-1 sensitivity by 6.3% in the overall population and by only 2.2% for patients with metastases. SCC determination should be considered an inefficient method as a potential diagnosing tool for NSCLC patients, and it provides no additional value when used in combination with CYFRA21-1.

Lung cancers in the early stages are sometimes detected incidentally. The aim of this study is to evaluate the outcome of patients with lung cancer detected incidentally and to compare to those in whom the malignancy was detected by symptoms. Untreated patients with lung cancer, who were admitted to our division over a 28-year period up to 2003, were analyzed with reference to their reasons for detection of the cancer. During the period, 1168 patients were diagnosed, and 173 (14.8%) of them were detected incidentally. As lung cancers detected incidentally were more often at operable stage (stage IA-IIIA) (p=0.0001), surgical treatment was chosen more frequently in the incidentally diagnosed group (p=0.0001). The outcome with lung cancer patients detected incidentally was more favorable than that of the patients detected by the symptoms (multivariate analysis, p=0.0001). The incidental detection of lung cancer contributes to improvement of the outcome. This study demonstrated a careful review of chest radiography obtained at routine or preoperative examination is important especially for the high-risk patients such as elderly and those with smoking history.

Gefitinib ("Iressa", ZD1839) is a selective epidermal growth factor receptor-tyrosine kinase inhibitor, which blocks signal transduction pathways implicated in proliferation and survival of cancer cells. However, in vitro and in vivo studies concerning cell growth after withdrawal of gefitinib are limited. To determine whether cancer cells would resume proliferation upon removal of gefitinib, an in vitro study was undertaken using 4 human non-small cell lung cancer cell lines. With immunocytochemical staining and Western blot analysis, we confirmed positive expression of EGFR in these cell lines. We next evaluated growth inhibition before and after withdrawal of gefitinib. After incubation with 0-100 microM gefitinib for 24 h, medium containing gefitinib was removed, followed by addition of fresh growth medium to cell cultures. MTT assays were performed daily over a 6-day time course. Even at very low levels of gefitinib (