Immunohistochemical markers of prognosis in non-small cell lung cancer: a review and proposal for a multiphase approach to marker evaluation

Characteristics of the tumour that affect and predict the survival outcome of patients with cancer are prognostic markers for cancer. In non-small cell lung carcinoma (NSCLC), stage is the main determinant of prognosis and the basis for deciding options for treatment. Patients with early-stage tumour are treated by complete surgical resection, which is curative in 40-70% of patients. That there are other factors important in determining the biology of these tumours, especially genes that have a role in metastasis, is indicated. Such factors could potentially be used to further classify patients into groups according to substages that may be treated differently. During the past decade, a large number of proteins that are putatively important in carcinogenesis and cancer biology have been studied for their prognostic value in NSCLC, but none of them have been proved to be sufficiently useful in clinical diagnosis. Several markers (epidermal growth factor receptor, human epidermal growth factor receptor 2, Ki-67, p53 and Bcl-2) have been studied exhaustively. Ki-67, p53 and Bcl-2 are suggested to be important but weak prognostic markers, by meta-analyses of the results. Cyclin E, vascular endothelial growth factor A, p16(INK4A), p27(kip1) and beta-catenin are promising candidates, but require further study in large randomised clinical trial samples by using standardised assays and scoring systems. Some issues and inconsistencies in the reported studies to date are highlighted and discussed. A guideline for a multi-phase approach for conducting future studies on prognostic immunohistochemistry markers is proposed here.     

Revisit on congenital bronchopulmonary vascular malformations: a haphazard branching theory of malinosculations and its clinical classification and implication.

We propose a haphazard branching theory to support the concept of bronchopulmonary malinosculations, and we apply this theory to classify congenital bronchopulmonary vascular malformation (BPVM) based on the anatomical results we have found. Between January 1990 and December 1997, a total of 22 pediatric patients (10 male and 12 female), aged 2 days to 14 years (median, 19.6 months), with congenital BPVM were enrolled in this retrospective study. Study modalities include the clinical features and plain chest films (n = 22) plus at least two of the following: echocardiography (n = 13), barium esophagraphy (n = 2), bronchoscopy (n = 4), contrast bronchography (n = 8), high-resolution direct coronal CT (n = 1) and electron beam or ultrafast CT (n = 1) of the chest, MRI (n = 10), MRA (n = 1), contrast cineangiocardiography (n = 9), surgery (n = 11), or autopsy (n = 2). The salient clinical features were recurrent lung infections in 14 patients, acute respiratory distress in 13, associated cardiovascular malformations in 8, dextroversion in 7, congestive heart failure in 7, dextrocardia in 4, and complex congenital heart diseases in 4. There were abnormal openings (malinosculations) of the pulmonary airway in 20 patients: to an artery in 12, to a vein in 8, and to the lung parenchyma in 9. These 22 patients with congenital BPVM can be classified into bronchial malinosculation (10 cases), arterial malinosculation (2 cases), and bronchoarterial malinosculation (10 cases). Congenital BPVM can be classified in terms of bronchopulmonary malinosculation based upon a haphazard branching theory, in which abnormal communications between two independent systems (primitive foregut system and aortic-pulmonary arch system) occurred coincidentally rather than causally.     

Quantitative processed images acquired by histogram-SNR imaging used to evaluate parenchymal heterogeneity in the liver

Purpose: To evaluate a new system for displaying processed images of liver parenchyma based on quantitative estimation of heterogeneity by texture analysis.Methods: We measured the signal to noise ratio, one of the first-order statistics in the histogram of enveloped amplitude of radio-frequency backscattered echoes, using a 3.75-MHz transducer with texture analysis in conjunction with a new method in which the small ROI (region of interest) is segmented into multiple layers to minimize the influence of tissue attenuation and beam diffraction. In our computerized system, gray-display and color-display images, two types of processed images, were produced from the visual intensity of each small ROI, which was based on its signal to noise ratio. We studied 10 cases of normal liver, 10 cases of fatty liver, and 10 cases of cirrhotic liver. The processed images obtained from these livers were reviewed to observe their features and to compare their usefulness in estimating the heterogeneity of the liver parenchyma with that of conventional B-mode images.Results: Gray-display images of cirrhotic livers appeared much blacker than the images produced from other disorders, and color-display images of cirrhotic liver appeared much bluer or greener than the others. Rate of correct diagnosis from B-mode images was 68.3 ±6.8%; from gray-display images, 85.8±7.4%; and from color-display images, 91.7±8.2%. Rate of correct assessment from B-mode images and gray-display images was significantly correlated (p=0.0015), as was rate of correct assessment from the B-mode images and the color-display images (p=0.0060).Conclusion: The processed images obtained using this computerized system contributed to the correct and objective interpretation of the heterogeneity of the liver parenchyma.