Image analysis framework for infection monitoring.

We present a novel framework for automatic extraction of the progress of an infection from time-series medical images, with application to pneumonia monitoring. In each image of a series, the lungs, which are the body components of interest in our study, are detected and delineated by a modified active shape model-based algorithm that is constrained by binary approximation masks. This algorithm offers resistance in the presence of infection manifestations that may distort the typical appearance of the body components of interest. The relative extent of the infection manifestations is assessed by supervised classification of samples acquired from the respective image regions. The samples are represented by multiple dissimilarity features fused according to a novel entropy-based weighted voting scheme offering nonparametric operation and robustness to outliers. The output of the proposed framework is a time series of structured data quantifying the relative extent of infection manifestations at the body components of interest over time. The results obtained indicate an improved performance over relevant state-of-the-art methods. The overall accuracy quantified by the area under receiver operating characteristic reaches 90.0 ± 2.1%. The effectiveness of the proposed framework to pneumonia monitoring, the generality, and the adaptivity of its methods open perspectives for application to other medical imaging domains.

Tuberculous effusion: ADA activity correlates with CD4+ cell numbers in the fluid and the pleura.

BACKGROUND: Adenosine deaminase (ADA) is a commonly used marker in the diagnosis of tuberculous effusion and there is evidence that its production is linked to T cells and monocytes. Data on the correlation between ADA and T cells or macrophages in tuberculous effusions are conflicting. Furthermore, no studies have examined a possible correlation between pleural tissue infiltration and ADA. OBJECTIVES: We undertook this study to examine cell subsets in the fluid and the pleura in tuberculous effusion and their correlation to ADA. The use of cell subsets as a marker in the differential diagnosis was also examined. METHODS: Pleural fluid from 36 patients with tuberculous and 34 patients with malignant effusion as well as pleural tissue biopsies from 16 patients with tuberculous pleurisy were examined. The APAAP and the avidin-biotin complex immunocytochemical methods were used to examine CD4+ T cells and macrophages (CD68+), while ADA activity was measured by the Giusti colorimetric method. RESULTS: Our results showed that, in pleural fluid, CD4+ cells and ADA were significantly higher in tuberculous compared to malignant effusion (p<0.001 for all measurements). In pleural tissue biopsies, macrophages were the predominant cells but CD4+ T cells were also abundant. A significant correlation was found between ADA and CD4+ numbers in pleural fluid and tissue (r=0.45, p<0.01; r=0.75, p<0.001, respectively). ADA had high sensitivity and specificity for differential diagnosis while cell subsets did not. CONCLUSIONS: These results indicate that ADA activity correlates to CD4+ T cell infiltration in the pleura and the fluid. Moreover, ADA but no cell subsets may be used as markers of tuberculous effusion.

Prognostic significance of pleural lavage cytology after resection for non-small cell lung cancer.

OBJECTIVE: In the staging of lung cancer, pleural effusion that is malignant on cytologic examination is regarded as T4 disease, and curative resection cannot be performed. We conducted this study to determine whether cancer cells can be present in the pleural cavity with no pleural effusion, to investigate the factors contributing to that occurrence, and to evaluate its prognostic significance. METHODS: Eighty-five patients (77 males, eight females) with a median age 60.1-+/--7.9 years (31--74 years) underwent a major lung resection, due to lung cancer in our department. From January 1998 to December 1999, 30 pneumonectomies, seven bilobectomies, 46 lobectomies and two wedge-resections were performed. Chest wall resection was performed in four patients. After performing a posterolateral thoracotomy and lung resection with extended mediastinal lymph node dissection, the pleural cavity was filled with 1 l physiologic saline solution (PSS) and the fluid was shaken. The lavage fluid was suctioned off (S1). Immediately after the lavage, the pleural cavity was refilled with 3 l PSS. The surgeon washed out the pleural cavity by hand for 1 min and the fluid was suctioned off. Finally, the pleural cavity was refilled with 1 l PSS and a new lavage fluid was suctioned off (S2). A cytologic examination was carried out for each sample. RESULTS: The pathology report showed 39 adenocarcinomas, 33 squamous-cell, two adenosquamous, four large-cell, two neuroendocrine and five undifferentiated carcinomas. S1 was positive in eight patients (9.4%), while S2 was positive in four patients (4.7%). The correlation of positive pleural lavage and infiltrated lymph nodes demonstrated a statistically significant relation between presence of N2 disease and positive S2 sample (P = 0.049). No significant correlation existed between positive lavage sample (S1 or S2) and TNM stage, level of T, extent of tumor invasion, kind of operation, histological type or differentiation of the cancer (Chi square test). The mean follow-up is 11.3 +/- 6.2 months (4--22 months). There are 78 patients alive. A significance difference in survival was identified in-patients with positive S1 (P = 0.0081), and positive S2 (P = 0.0251) (Kaplan--Meier). CONCLUSION: The cytologic results of lavage were positive for malignant cells in eight of 85 patients (9.4%). The existence of cancer cells in the pleural cavity can be the result of their exfoliation or surgical manipulations. The mechanical irrigation subdivides the percentage of positive samples. Our study supports that the positive findings on pleural lavage cytology is an essential prognostic factor.

Combined expression of p53, Bcl-2, and p21WAF-1 proteins in lung cancer and premalignant lesions: association with clinical characteristics.

We examined p53, p21WAF-1, and Bcl-2 protein expression in malignant and nonmalignant bronchial specimens obtained during bronchoscopy from 60 lung cancer patients. Twenty-six (43.3%), 36 (60%), and 20 (33.3%) of the tumors were p53, p21WAF-1, and Bcl-2 positive, respectively. High-level p53 and Bcl-2 expression characterized advanced preneoplastic lesions, while hyperplasias, squamous metaplasias, and mild dysplasias exhibited low levels of expression. There was no difference between early and advanced preneoplastic lesions in the level of p21WAF-1, expression. A history of heavy smoking was associated with p21WAF-1, expression in preneoplastic lesions (p = 0.022) and tumors (p = 0.032). p53(-)/p21WAF-1(++)/bcl-2(-) was the only significant independent predictor of lower clinical stage (OR: 0.88, p = 0.038). In univariate analysis, survival of NSCLC patients was affected by disease stage (p <0.001) and tumor histology (p = 0.018). While single-protein expression was not associated with prognosis, the combined immunophenotype p53(-)/p21WAF-1(++)/bcl-2(-) predicted longer survival (p = 0.03). In multivariate analysis, only the TNM stage was found to be a prognostic factor for NSCLC. We conclude that p53 and Bcl-2 alterations may happen early in bronchial carcinogenesis and that absence of these alterations in combination with p21WAF-1, overexpression may be associated with a less aggressive tumor behavior.

Distant cutaneous metastasis from carcinoma of the uterus. A case report.

Cutaneous metastasis from intraabdominal carcinoma is relatively rare. When it is present it is usually located in the skin overlying the neoplasm [1]. Carcinoma of the uterus metastatic to the skin accounts for 9% of all cutaneous metastases. Distant metastasis is extremely rare. Such a metastasis to the skin of the big toe of the lower limb is presented.

Expression of mdm-2 protein in neoplastic, preneoplastic, and normal bronchial mucosa specimens: comparative study with p53 expression.

Loss of function of the p53 tumor supressor gene is involved in nearly all human cancer. Recently a cellular oncogene product, mdm2, has been shown to bind to p53 and eliminate its ability to function as a transcription factor. mdm2 and p53 immunohistochemical protein expression was studied in tumor tissues, preneoplastic lesions, and normal bronchial mucosa. The specimens were obtained during diagnostic bronchoscopy from 53 patients with lung cancer. In the tumor specimens, p53 nuclear staining was detected in 26 (49%) cases, mdm2 in 11 (20.7%), and simultaneous expression of both proteins in 6 (11.3%) cases. Thirty-five sections with preneoplastic lesions were found in 21 patients. p53 nuclear staining was found in 11 of 35 and mdm2 in 6 of 35 sections. In normal cells, mdm2 positive staining was found in 18 and p53 in 12 specimens. Simultaneous p53 and mdm2 expression was found in 4 specimens. Our results indicate that p53 expression is more frequent than mdm2 expression in lung cancer tissues. Alterations in these proteins are early events and may represent alternative pathways in carcinogenesis.

Immunohistochemical detection of p53 protein in neoplastic, preneoplastic and normal bronchial mucosa specimens obtained during diagnostic bronchoscopy.

The expression of p53 protein was evaluated immunochemically in cancer tissue, preneoplastic lesions and normal bronchial mucosa obtained during diagnostic bronchoscopy from 53 patients with lung cancer and 12 patients with benign lung diseases. In lung cancer patients, positive p53 staining was detected in 26/53 (49%) of the tumour specimens. In preneoplastic lesions p53 positive staining was found in 8 of 24 (33.3%) squamous metaplasia, 1 of 4 hyperplasia and 1 of 3 dysplasia lesions. In the same group of patients, 12 cases were found with positive p53 cells in normal bronchial mucosa. In patients with benign diseases, positive p53 staining was found in 1 of 4 cases with squamous metaplasia and in one normal mucosa. Our results provide evidence that somatic genetic alterations may occur in early stages of lung tumorigenesis, raising the possibility that molecular analyses is useful in the early diagnosis of precancerous lesions of the bronchial mucosa, and results indicate that p53 expression can be studied in small tissue specimens obtained during bronchoscopy.

Expression of the c-myc oncoprotein in human metaplastic epithelial cells of fibrocystic disease.

Sections derived from fibrocystic disease in human breast tissue were examined for the presence of the c-myc oncoprotein by using the c-myc specific monoclonal antibody 9E10 (1). The results obtained revealed that the c-myc gene was not expressed in normal epithelial cells either of ducts or lobules. It was expressed mainly in mucous metaplastic cells and very rarely in apocrine cells. The c-myc protein was observed at a higher level in mucous metaplastic cells of epitheliosis and multiple papillomas. The number and intensity of positive mucous metaplastic cells was significantly increased after pretreating the sections with neuraminidase. We suggest that elevated expression of the c-myc nuclear oncoprotein in human breast metaplastic epithelial cells play a role in the early stages of malignant cell transformation.