Association of specific metastatic organs with the prognosis and chemotherapeutic response in patients with advanced lung cancer.

BACKGROUND: This study was performed to investigate the influence of specific metastatic organs on the prognosis and therapeutic effect in patients with advanced lung cancer. METHODS: We retrospectively analyzed 400 patients with pathologically diagnosed advanced lung cancer to determine the association of the patients' metastatic status with their prognoses and responses to first-line therapy. Metastases within the chest cavity (pulmonary metastasis, pleural effusion, and pericardial effusion) were counted as one organ. RESULTS: The numbers of metastatic organs in the patients were as follows: one (n=199 patients), two (n=99), three (n=61), and four or more (n=41). A multivariate analysis showed that liver and muscle metastases were independently associated with shorter overall survival (median of 207 and 120 days, respectively) and shorter progression-free survival (median of 125 and 53 days, respectively). Chest cavity, bone, brain, and lymph node metastases were not associated with survival. The presence of either muscle or skin metastasis was associated with a lower response rate to first-line therapy than was the absence of each metastasis (14.3% vs. 49.4% and 11.1% vs. 48.9% in patients with vs. without muscle or skin metastasis, respectively). CONCLUSIONS: Muscle and liver metastases were associated with poor outcomes. Muscle and skin metastases were associated with a lower response rate to treatment. For patients with advanced lung cancer, oncologists should select treatment strategies considering the patients' metastatic statuses as well as other clinical characteristics.

Ulcerative interstitial cystitis in an adolescent successfully treated with complete transurethral ulcer resection: A case report.

INTRODUCTION: Interstitial cystitis is difficult to treat and may affect adolescents. CASE PRESENTATION: A 15-year-old girl presented with severe pain upon terminal micturition that persisted for approximately 2 hours. The pain had been present for more than 1 month. Cystoscopy revealed severe erosion throughout the trigone. Transurethral fulguration did not improve her symptoms. However, complete electric resection of the ulcer markedly reduced the symptom. After complete resection, pain on urination disappeared and she has had no pain without medication for 15 months. CONCLUSION: Complete resection not fulguration of the ulcer is effective for interstitial cystitis in adolescent female patients.

Serum CYFRA 21-1 but not Vimentin is Associated with Poor Prognosis in Advanced Lung Cancer Patients.

BACKGROUND: Cytokeratins and Vimentin are intermediate filament proteins. Vimentin expression in tissue samples has been reported to be associated with a poor prognosis in non-small cell lung cancer patients who underwent surgery. CYFRA 21-1 (Cytokeratin 19 Fragment) is a well known tumor marker. OBJECTIVE: This study aimed to investigate the usefulness of serum vimentin as a tumor marker and significance of CYFRA 21-1 and vimentin expression on prognosis of advanced lung cancer patients. METHODS: One hundred and four advanced lung cancer patients and 19 non-lung cancer patients were included. A total of 157 clinical samples obtained from 113 patients was used for immunostaining of vimentin and measurements of CYFRA 21-1 and vimentin concentrations. RESULTS: Compared to low concentration, high concentration of serum CYFRA 21-1 was associated with shorter overall survival in lung cancer patients. However, there was no difference in the serum vimentin concentration between the patients with lung cancer and those with non-lung cancer. No difference in vimentin concentration was observed between the malignant and non-malignant pleural effusions. Immunostaining revealed that of the 43 tumor samples, 21 were positive and 22 were negative for vimentin. No significant difference was found in overall survival between patients with positive and negative for vimentin. CONCLUSION: An elevated serum CYFRA 21-1 concentration was associated with shorter overall survival in advanced lung cancer patients. However, serum vimentin was not as useful as a tumor marker of lung cancer. The vimentin positivity in tumor samples might not predict patients' prognosis in patients with advanced lung cancer.

[RESULTS OF TONSILLECTOMY AND STEROID PULSE THERAPY IN 20 CASES OF RECURRENT IgA NEPHROPATHY AFTER KIDNEY TRANSPLANTATION].

(Background) The standard treatment for recurrent immunoglobulin A nephropathy (rIgAN) after kidney transplantation (KTx) has not been established. (Methods) The results of treatment consisting of tonsillectomy and steroid pulse therapy in 20 recipients who were diagnosed as rIgAN were retrospectively analyzed. (Results) The level of proteinuria significantly decreased from 0.84±0.81 g/day to 0.27±0.31 g/day after treatment (P=0.007). Microscopic hematuria disappeared or improved in 58.3% and 66.6% of recipients 6 and 12 months after treatment, respectively. Serum creatinine levels remained stable for 5 years by the treatment, except for 3 cases of graft loss. Sixteen recipients received renal graft biopsies before and after treatment. Mesangial IgA deposition were dramatically decreased in 7 recipients (43.75%). The degree of mesangial hypercellularity, endocapillary hypercellularity, and crescents formation improved in 3 (18.8%), 6 (37.5%), and 4 (25%) recipients after treatment. (Conclusion) Steroid pulse therapy combined with tonsillectomy may be clinically and histopathologically effective treatment for rIgAN after KTx.

Clinical features of patients with lung cancer accompanied by thromboembolism or disseminated intravascular coagulation.

PURPOSE: Thromboembolism (TE) and disseminated intravascular coagulation (DIC) are often present concomitantly. This study aimed to investigate the clinical features of patients with lung cancer and TE and/or DIC. PATIENTS AND METHODS: Data on 716 patients with pathologically confirmed diagnoses of lung cancer were retrospectively analyzed for TE/DIC. RESULTS: TE was identified in 16 patients (2.2%) and DIC was identified in 5 (0.7%) during the diagnosis of cancer. TE was more often observed in adenocarcinoma (4.0%). Both TE and DIC were more often observed in stage IV (4.7% and 1.5%, respectively). In patients with stage IV adenocarcinoma who received some systemic treatment, overall survival (OS) was significantly shorter in patients with TE (median 280 days) and with DIC (72 days) than in non-TE/DIC patients (538 days). Multivariate analysis showed that older age, poor performance status, greater number of metastatic organs, no EGFR mutation/ALK fusion, presence of interstitial lung disease, and DIC were poor prognostic factors for OS. In 339 patients in stage IV, 25 (7.4%) and 21 (6.2%) patients had TE and DIC, respectively, during the course. Six patients exhibited both TE and DIC. TE was more often observed in adenocarcinoma (20 of 196 patients; 10.2%). Patients with DIC had extremely shorter survival (median 13 days) after onset. Cancer control by systemic therapy, such as chemotherapy and molecular-targeted therapy, contributed to long survival. CONCLUSION: Patients with TE/DIC had shorter OS than patients without TE/DIC. Control of lung cancer by systemic therapy was important for longer survival after the onset of events.

Phanerochaete sordida as a cause of pulmonary nodule in an immunocompromised patient: a case report.

BACKGROUND: Phanerochaete sordida is a species of wood rotting fungus, which can degrade lignin, cellulose and hemicellulose contained in wood and other hard-to-biodegrade organic substances. However, to date, there have been no other reports demonstrating that P. sordida can infect humans. CASE PRESENTATION: A 66-year-old Japanese man presented for a mass increasing in size on his left thigh. He had been suffering from rheumatoid arthritis for 18 years and chronic obstructive pulmonary disease for 20 years, for which he was being treated with 5 mg/day prednisolone and 8 mg/week methotrexate. The mass resection was performed two months later, and was diagnosed as malignant fibrous histiocytosis. However, a computed tomography examination for tumor recurrence after surgery showed a newly emergent pulmonary nodule. We therefore decided to resect the nodule by thoracoscopic procedure. Histopathological examination of the excised specimen showed that the lesion was a granuloma, with necrotic tissue and clumping of Aspergillus-like hyphae. Therefore, the nodule was diagnosed as a fungal infection and tissue specimens were cultured microbiologically. However, fungal growth was not observed. We consequently performed genetic analysis using a broad-range polymerase chain reaction. The 28S rRNA sequence demonstrated 100% homology with P. sordida using the NCBI BLAST program against the GenBank DNA databases. CONCLUSIONS: Using broad-range polymerase chain reaction, we identified P. sordida as the causative agent of a pulmonary nodule. These findings indicate that P. sordida may be an additional opportunistic causative organism of pulmonary infection in immunocompromised patients.

An autopsy case of bronchiolitis obliterans as a previously unrecognized adverse event of afatinib treatment.

Interstitial lung disease is a well-known pulmonary adverse event that occurs during epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy and results in restrictive ventilatory dysfunction. However, obstructive changes such as those associated with bronchiolitis obliterans (BO) have never been reported as adverse events resulting from the use of any approved EGFR-TKI. This report documents an autopsy case of BO that developed during afatinib treatment for adenocarcinoma of the lung. Knowledge of the possibility of this fatal adverse event is important for adequate follow-up of patients with lung cancer undergoing afatinib treatment.

Impact of idiopathic pulmonary fibrosis on advanced non-small cell lung cancer survival.

PURPOSE: The clinical features of patients with advanced non-small cell lung cancer (NSCLC) and interstitial lung disease (ILD) have not fully been elucidated. This study aimed to investigate the clinical features of these patients, particularly with idiopathic pulmonary fibrosis (IPF). METHODS: Data on 218 patients with pathologically confirmed diagnoses of NSCLC who had been treated with chemotherapy and/or molecular targeted therapy were retrospectively analyzed for progression-free survival (PFS), overall survival (OS), responses to first-line therapy, and incidence of acute exacerbations (AEs). RESULTS: Fifty-three of the 218 patients were diagnosed with ILD, and 34 of them with IPF. The frequency of epidermal growth factor receptor (EGFR) mutation was significantly lower in ILD and IPF patients than in non-ILD patients (2 or 0 vs. 32 %, respectively). Median PFS and OS were significantly shorter in both ILD and IPF patients than in non-ILD patients (118, 92, and 196 days for PFS, and 267, 223, and 539 days for OS, respectively). Multivariate analysis showed that poor performance status, absence of EGFR mutation, and presence of IPF were poor prognostic factors for PFS and OS. Disease control rate (DCR) was significantly lower in ILD and IPF patients than in non-ILD patients regardless of the presence of EGFR mutation (67 or 53 vs. 85 %, respectively). The incidence of AEs of ILD was significantly higher during chemotherapy with docetaxel-containing regimens (seven of 38; 18.4 %). CONCLUSIONS: Both IPF and ILD were associated with lower EGFR positivity, lower DCR, and shorter PFS and OS in advanced NSCLC patients.

Vimentin Regulates Invasiveness and Is a Poor Prognostic Marker in Non-small Cell Lung Cancer.

BACKGROUND: Lung cancer cells often express vimentin. However, the function of vimentin in lung cancer cells has not been fully evaluated. MATERIALS AND METHODS: We evaluated the association between vimentin expression in resected non-small cell lung cancer (NSCLC) specimens and prognosis. Short-interfering RNA targeting vimentin and establishment of an invasive cell line by repeated selection of invasive cells using a Matrigel membrane invasion chamber system (MICS) were performed. MICS was used to reveal the relationship between invasiveness and vimentin. RESULTS: Vimentin positivity was significantly associated with a poor prognosis and was significantly lower in squamous cell carcinoma than in adenocarcinoma. In in vitro experiments, silencing of vimentin reduced invasiveness. Highly invasive cell lines exhibited higher expression of vimentin than did parental cells, and invasive ability was reduced by knockdown of vimentin. CONCLUSION: Vimentin expression is associated with prognosis via alteration of the invasive ability of NSCLC cells.

Confluence-dependent resistance to cisplatin in lung cancer cells is regulated by transforming growth factor-beta.

PURPOSE OF THE STUDY: Confluence-dependent resistance (CDR) is a phenomenon in which the efficacy of anti-cancer agents decreases when cell density increases. CDR in lung cancer has never been reported. The purpose of this study is to investigate if CDR can occur in NSCLC cells and to find a role for transforming growth factor (TGF)-ß as a mechanism of CDR. MATERIALS AND METHODS: Non-small cell lung cancer (NSCLC) cell lines A549 and H2228 were exposed to cisplatin in a variety of cell density conditions. RNA interference targeting TGF-ß receptor I was performed to silence the TGF-ß pathway. RESULTS: CDR to cisplatin was induced in NSCLC cells, whereas CDR to crizotinib, an inhibitor of activin receptor-like kinase, was not observed. During confluent conditions, the TGF-ß1 concentration in the culture medium was the highest. Exogenous TGF-ß1 inhibited cell proliferation and reduced sensitivity to cisplatin. Inhibition of the TGF-ß pathway increased in terms of sensitivity to cisplatin at confluency. CONCLUSIONS: CDR to cisplatin can occur in NSCLC cells, and the TGF-ß pathway is associated with the regulation of CDR.

Air-leak Syndrome by Pleuroparenchymal Fibroelastosis after Bone Marrow Transplantation.

Objective Air-leak syndrome (ALS) is a life-threatening pulmonary complication following allogeneic bone marrow transplantation (allo-BMT) which is thought to be associated with graft-versus-host disease (GVHD). Recently, it has been reported that pleuroparenchymal fibroelastosis (PPFE) also occurs after allo-BMT and often causes ALS. We sought to extract common features of ALS caused by PPFE after allo-BMT. Methods The clinical data of patients who developed ALS caused by PPFE after undergoing allo-BMT (ALS-PPFE) between April 1996 and December 2007 at our institution were collected and reviewed retrospectively. The clinical findings, radiological and pathological features and treatment outcomes of ALS-PPFE were assessed. Results Five patients who developed ALS had histologically proven PPFE (four men, one woman: median age, 37 years). The age of onset of ALS-PPFE was 13 to 109 months (median, 68.8 months) after BMT. Alkylating agents were used as conditioning chemotherapy for BMT in all patients. Only one patient developed chronic GVHD (limited type). The common radiological findings were subpleural thickening and traction bronchiectasis predominantly in the bilateral upper lung fields. The histological pulmonary specimens showed no findings of bronchiolitis obliterans or GVHD. Immunosuppressive therapy was not effective in any of the cases, and all patients died of respiratory failure with or without lung transplantation. Conclusion ALS-PPFE is an extremely late-onset noninfectious pulmonary complication of allo-BMT. This complication is progressive, resistant to immunosuppressive treatment and has a poor prognosis. No association was found between PPFE and GVHD.

Transbronchial Dissemination of Squamous Cell Lung Cancer.

We report a case of squamous cell lung cancer with transbronchial dissemination in a 73-year-old man. Bronchoscopic examination revealed multiple bronchial mucosal nodules that existed independently of one another. We reviewed 16 previous cases of endobronchial metastasis in lung cancer. All patients were men. Among the reports that described the smoking history, most patients were smokers (6/7), and the most frequent histological type of cancer was squamous cell carcinoma (11/17). Although hematogenous and lymphogenous routes have been reported as metastatic mechanisms, no previous cases involving transbronchial dissemination have been described. Transbronchial dissemination may be an alternative pathway of endobronchial metastasis.

Squamous Cell Lung Cancer Associated With Systemic Sclerosis.

We here describe a 50-year-old woman diagnosed with squamous cell lung cancer (SqLC) with underlying interstitial lung disease (ILD) 14 years after a diagnosis of systemic sclerosis (SSc). We reviewed the literature and collected 21 well-documented cases with SqLC associated with SSc including the present case. Several characteristics of SqLC associated with SSc have been found. First, the average age at diagnosis of SqLC is 57 years, which is much younger than that reported for patients without SSc. Second, SqLC could occur even in never or light smokers, although SqLC usually has a strong association with smoking history. Third, two-thirds of the available cases have ILD. In addition, SqLC developed in the area of ILD in most cases with ILD. Fourth, SqLC generally occurs after a long period from the diagnosis of SSc; the average of this interval reaches 12 years. It would be helpful to know these features so that physicians follow up and treat SSc patients adequately.

Anaplastic lymphoma kinase gene analysis as a useful tool for identifying primary unknown metastatic lung adenocarcinoma.

A 55-year-old woman was admitted for an evaluation of a mediastinal mass, bilateral cervical lymphadenopathy and a left breast tumor. Although pathology revealed a diagnosis of breast cancer, the cervical lymph nodes differed from the breast lesion. An anaplastic lymphoma kinase (ALK) gene analysis revealed ALK rearrangement in the cervical lymph nodes only, which were therefore diagnosed as reflective of metastasis of lung adenocarcinoma. The mediastinal tumor was also diagnosed as an ALK-positive lung adenocarcinoma based on its therapeutic response. ALK gene analyses can be used to identify primary lesions in patients with cancers of unknown primary sites.

Increases in serum CYFRA21-1 concentration during successful treatment with crizotinib.

BACKGROUND: Increases in tumor marker concentrations usually suggest disease progression. CASE REPORT: We here describe on 3 patients with non-small cell lung cancer whose serum concentrations of CYFRA21-1 increased in spite of successful treatment with crizotinib. Discontinuation of crizotinib resulted in a rapid decrease in serum CYFRA21-1 concentrations in all cases. In 1 patient with progressive disease, in spite of increasing the dose of crizotinib, CYFRA21-1 concentrations decreased. CONCLUSIONS: Crizotinib can induce increases in CYFRA21-1 concentration without disease progression. Pulmonologists and oncologists should be aware of this novel phenomenon, and focus on interpretation of CYFRA21-1 concentrations in monitoring tumor response to crizotinib treatment.

Higher susceptibility of NOD/LtSz-scid Il2rg (-/-) NSG mice to xenotransplanted lung cancer cell lines.

PURPOSE: No lung cancer xenograft model using non-obese diabetic (NOD)-scid Il2rg (-/-) mice has been reported. The purpose of this study is to select a suitable mouse strain as a xenogenic host for testing tumorigenicity of lung cancer. MATERIALS AND METHODS: We directly compared the susceptibility of four immunodeficient mouse strains, c-nu, C.B-17 scid, NOD-scid, and NOD/LtSz-scid Il2rg (-/-) (NSG) mice, for tumor formation from xenotransplanted lung cancer cell lines. Various numbers (10(1)-10(5) cells/head) of two lung cancer cell lines, A549 and EBC1, were subcutaneously inoculated and tumor sizes were measured every week up to 12 weeks. RESULTS: When 10(4) EBC1 cells were inoculated, no tumor formation was observed in BALB/c-nu or C.B-17 scid mice. Tumors developed in two of the five NOD-scid mice (40%) and in all the five NSG mice (100%). When 10(3) EBC1 cells were injected, no tumors developed in any strain other than NSG mice, while tumorigenesis was achieved in all the five NSG mice (100%, P=0.0079) within 9 weeks. NSG mice similarly showed higher susceptibility to xenotransplantation of A549 cells. Tumor formation was observed only in NSG mice after inoculation of 10(3) or fewer A549 cells (40% vs 0% in 15 NSG mice compared with others, respectively, P=0.0169). We confirmed that the engrafted tumors originated from inoculated human lung cancer cells by immunohistochemical staining with human cytokeratin and vimentin. CONCLUSION: NSG mice may be the most suitable strain for testing tumorigenicity of lung cancer, especially if only a few cells are available.

Paraneoplastic syndromes associated with lung cancer.

Paraneoplastic syndromes are signs or symptoms that occur as a result of organ or tissue damage at locations remote from the site of the primary tumor or metastases. Paraneoplastic syndromes associated with lung cancer can impair various organ functions and include neurologic, endocrine, dermatologic, rheumatologic, hematologic, and ophthalmological syndromes, as well as glomerulopathy and coagulopathy (Trousseau's syndrome). The histological type of lung cancer is generally dependent on the associated syndrome, the two most common of which are humoral hypercalcemia of malignancy in squamous cell carcinoma and the syndrome of inappropriate antidiuretic hormone secretion in small cell lung cancer. The symptoms often precede the diagnosis of the associated lung cancer, especially when the symptoms are neurologic or dermatologic. The proposed mechanisms of paraneoplastic processes include the aberrant release of humoral mediators, such as hormones and hormone-like peptides, cytokines, and antibodies. Treating the underlying cancer is generally the most effective therapy for paraneoplastic syndromes, and treatment soon after symptom onset appears to offer the best potential for symptom improvement. In this article, we review the diagnosis, potential mechanisms, and treatments of a wide variety of paraneoplastic syndromes associated with lung cancer.

Membranous glomerulonephritis associated with Mycobacterium shimoidei pulmonary infection.

PATIENT: Male, 83 FINAL DIAGNOSIS: Membranous glomerulonephritis Symptoms: Producting cough Medication: - Clinical Procedure: - Specialty: Nephrology. OBJECTIVE: Rare disease. BACKGROUND: Membranous glomerulonephritis can occur secondarily from infectious diseases. There are no reports describing membranous glomerulonephritis caused by non-tuberculous mycobacterium infection. However, several cases with membranous glomerulonephritis due to Mycobacterium tuberculosis have been reported. Mycobacterium shimoidei is an uncommon pathogen, and less than 20 cases with this species have been reported. A therapeutic regimen for this infection has not been established yet. CASE REPORT: An 83-year-old Japanese man presented with productive cough for 6 months. Computed tomography scan showed multiple cavities in the bilateral pulmonary fields. Acid-fast bacilli were evident in his sputum by Ziehl-Neelsen staining (Gaffky 3). PCR amplifications for Mycobacterium tuberculosis, Mycobacterium avium, and Mycobacterium intracellulare were all negative. Finally, Mycobacterium shimoidei was identified by rpoB sequencing and 16S rRNA sequencing. Urine examination showed a sub-nephrotic range of proteinuria and histology of the kidney showed membranous glomerulonephritis. Antimycobacterial treatment with clarithromycin, rifampicin, and ethambutol dramatically improved not only the pulmonary disease, but also the proteinuria. CONCLUSIONS: To the best of our knowledge, the presented case is the first report showing non-tuberculous mycobacterium-induced secondary membranous glomerulonephritis. A combination with clarithromycin, ethambutol, and rifampicin might be effective for treatment of Mycobacterium shimoidei infection.

Paraneoplastic focal segmental glomerulosclerosis in a patient with lung adenocarcinoma.

Focal segmental glomerulosclerosis (FSGS) is extremely rare among paraneoplastic nephrotic syndromes. We herein report a case of lung adenocarcinoma with nephrotic syndrome caused by paraneoplastic FSGS. A 68-year-old man visited our hospital for an evaluation of a right hilar mass on chest radiography and supraclavicular lymphadenopathy. Because an aspiration biopsy of the supraclavicular lymph node revealed adenocarcinoma, the patient was diagnosed with lung adenocarcinoma. He also had nephrotic syndrome, and the pathological findings of the renal biopsy demonstrated FSGS. Standard-dose carboplatin-containing chemotherapy led to a partial response for lung cancer and improved the patient's nephrotic syndrome without causing any adverse renal effects.