Biomedical subjects

P W Hamilton

Publications and source records attributed to P W Hamilton.

At least 19 recordsLinked to original sources

PubMed2006

Non-invasive in vivo imaging in small animal research.

Non-invasive real time in vivo molecular imaging in small animal models has become the essential bridge between in vitro data and their translation into clinical applications. The tremendous development and technological progress, such as tumour modelling, monitoring of tumour growth and detection of metastasis, has facilitated translational drug development. This has added to our knowledge on carcinogenesis. The modalities that are commonly used include Magnetic Resonance Imaging (MRI), Computed Tomography (CT), Positron Emission Tomography (PET), bioluminescence imaging, fluorescence imaging and multi-modality imaging systems. The ability to obtain multiple images longitudinally provides reliable information whilst reducing animal numbers. As yet there is no one modality that is ideal for all experimental studies. This review outlines the instrumentation available together with corresponding applications reported in the literature with particular emphasis on cancer research. Advantages and limitations to current imaging technology are discussed and the issues concerning small animal care during imaging are highlighted.

Animals↗

PubMed2005

Phenotypic changes in mitochondrial membrane potential (Delta psi(m)) during valinomycin-induced depolarisation and apoptosis.

A large body of evidence has implicated mitochondria in control of cell death, where key apoptotic mechanisms involve change in mitochondrial membrane permeability and depolarisation of mitochondrial membrane potential (Delta psi(m)). Assessment of Delta psi(m) is traditionally conducted using the lipophilic cation JC-1 on the flow cytometer or by fluorescent microscopy. Here we assess JC-1 aggregation using the novel tool of digital texture analysis to establish mitochondrial phenotypic changes induced by the K+ ionophore, valinomycin in a unique model comprising SW480 and SW620 cell lines. This provides an opportunity to study these phenomena in the context of colorectal cancer. Valinomycin-induced apoptosis was detected using morphology and analysis of DNA content. Cells were treated with valinomycin, images digitally recorded on a calibrated video photometer and subjected to high resolution digital texture analysis. This demonstrated that the HARAM texture features (Mean of the Haralick texture features) were highly valuable in describing the transition of Delta psi(m) as the cell undergoes apoptosis. In conclusion this study illustrates the potential of texture analysis as a novel and additional technique for quantifying JC-1 aggregation and revealing the spectrum of collapse of Delta psi(m) during apoptosis.

Apoptosis↗

PubMed2004

Karyometry detects subvisual differences in chromatin organisation state between non-recurrent and recurrent papillary urothelial neoplasms of low malignant potential.

AIM: To analyse nuclear chromatin texture in non-recurrent and recurrent papillary urothelial neoplasms of low malignant potential (PUNLMPs). MATERIALS: Ninety three karyometric features were analysed on haematoxylin and eosin stained sections from 20 PUNLMP cases: 10 from patients with a solitary PUNLMP lesion, who were disease free during at least eight years' follow up, and 10 from patients with unifocal PUNLMP, one or more recurrences being seen during follow up. RESULTS: Kruskal-Wallis analysis was used to search for features showing significant differences between recurrent and non-recurrent cases. Significance was better than p<0.005 for more than 20 features. Based on significance, six texture features were selected for discriminant analysis. Stepwise linear discriminant analysis reduced Wilk's lambda to 0.87, indicating a highly significant difference between the two multivariate data sets, but only modest ability to discriminate (70% correct case classification). A box sequential classifier was used based on data derived from discriminant analysis. The classifier took three classification steps and classified 19 of the 20 cases correctly (95% correct case classification). To determine whether significant case grouping could also be obtained based on an objective criterion, the merged data sets of non-recurrent and recurrent cases were submitted to the unsupervised learning algorithm P-index. Two clusters were formed with significant differences. The subsequent application of a Cooley/Lohnes classifier resulted in an overall correct case classification rate of 85%. CONCLUSIONS: Karyometry and multivariate analyses detect subvisual differences in chromatin organisation state between non-recurrent and recurrent PUNLMPs, thus allowing identification of lesions that do or do not recur.

Algorithms↗

PubMed2003

Computerized diagnostic decision support system for the classification of preinvasive cervical squamous lesions.

Previous studies have revealed considerable interobserver and intraobserver variation in the histological classification of preinvasive cervical squamous lesions. The aim of the present study was to develop a decision support system (DSS) for the histological interpretation of these lesions. Knowledge and uncertainty were represented in the form of a Bayesian belief network that permitted the storage of diagnostic knowledge and, for a given case, the collection of evidence in a cumulative manner that provided a final probability for the possible diagnostic outcomes. The network comprised 8 diagnostic histological features (evidence nodes) that were each independently linked to the diagnosis (decision node) by a conditional probability matrix. Diagnostic outcomes comprised normal; koilocytosis; and cervical intraepithelial neoplasia (CIN) I, CIN II, and CIN III. For each evidence feature, a set of images was recorded that represented the full spectrum of change for that feature. The system was designed to be interactive in that the histopathologist was prompted to enter evidence into the network via a specifically designed graphical user interface (i-Path Diagnostics, Belfast, Northern Ireland). Membership functions were used to derive the relative likelihoods for the alternative feature outcomes, the likelihood vector was entered into the network, and the updated diagnostic belief was computed for the diagnostic outcomes and displayed. A cumulative probability graph was generated throughout the diagnostic process and presented on screen. The network was tested on 50 cervical colposcopic biopsy specimens, comprising 10 cases each of normal, koilocytosis, CIN I, CIN II, and CIN III. These had been preselected by a consultant gynecological pathologist. Using conventional morphological assessment, the cases were classified on 2 separate occasions by 2 consultant and 2 junior pathologists. The cases were also then classified using the DSS on 2 occasions by the 4 pathologists and by 2 medical students with no experience in cervical histology. Interobserver and intraobserver agreement using morphology and using the DSS was calculated with kappa statistics. Intraobserver reproducibility using conventional unaided diagnosis was reasonably good (kappa range, 0.688 to 0.861), but interobserver agreement was poor (kappa range, 0.347 to 0.747). Using the DSS improved overall reproducibility between individuals. Using the DSS, however, did not enhance the diagnostic performance of junior pathologists when comparing their DSS-based diagnosis against an experienced consultant. However, the generation of a cumulative probability graph also allowed a comparison of individual performance, how individual features were assessed in the same case, and how this contributed to diagnostic disagreement between individuals. Diagnostic features such as nuclear pleomorphism were shown to be particularly problematic and poorly reproducible. DSSs such as this therefore not only have a role to play in enhancing decision making but also in the study of diagnostic protocol, education, self-assessment, and quality control.

Bayes Theorem↗

PubMed2002

Expert system support using a Bayesian belief network for the classification of endometrial hyperplasia.

Accurate morphological classification of endometrial hyperplasia is crucial as treatments vary widely between the different categories of hyperplasia and are dependent, in part, on the histological diagnosis. However, previous studies have shown considerable inter-observer variation in the classification of endometrial hyperplasias. The aim of this study was to develop a decision support system (DSS) for the classification of endometrial hyperplasias. The system used a Bayesian belief network to distinguish proliferative endometrium, simple hyperplasia, complex hyperplasia, atypical hyperplasia and grade 1 endometrioid adenocarcinoma. These diagnostic outcomes were held in the decision node. Four morphological features were selected as diagnostic clues used routinely in the discrimination of endometrial hyperplasias. These represented the evidence nodes and were linked to the decision node by conditional probability matrices. The system was designed with a computer user interface (CytoInform) where reference images for a given clue were displayed to assist the pathologist in entering evidence into the network. Reproducibility of diagnostic classification was tested on 50 cases chosen by a gynaecological pathologist. These comprised ten cases each of proliferative endometrium, simple hyperplasia, complex hyperplasia, atypical hyperplasia and grade 1 endometrioid adenocarcinoma. The DSS was tested by two consultant pathologists, two junior pathologists and two medical students. Intra- and inter-observer agreement was calculated following conventional histological examination of the slides on two occasions by the consultants and junior pathologists without the use of the DSS. All six participants then assessed the slides using the expert system on two occasions, enabling inter- and intra-observer agreement to be calculated. Using unaided conventional diagnosis, weighted kappa values for intra-observer agreement ranged from 0.645 to 0.901. Using the DSS, the results for the four pathologists ranged from 0.650 to 0.845. Both consultant pathologists had slightly worse weighted kappa values using the DSS, while both junior pathologists achieved slightly better values using the system. The grading of morphological features and the cumulative probability curve provided a quantitative record of the decision route for each case. This allowed a more precise comparison of individuals and identified why discordant diagnoses were made. Taking the original diagnoses of the consultant gynaecological pathologist as the 'gold standard', there was excellent or moderate to good inter-observer agreement between the 'gold standard' and the results obtained by the four pathologists using the expert system, with weighted kappa values of 0.586-0.872. The two medical students using the expert system achieved weighted kappa values of 0.771 (excellent) and 0.560 (moderate to good) compared to the 'gold standard'. This study illustrates the potential of expert systems in the classification of endometrial hyperplasias.

Bayes Theorem↗

PubMed2002

Transcontinental communication and quantitative digital histopathology via the Internet; with special reference to prostate neoplasia.

OBJECTIVE: To describe practical experiences in the sharing of very large digital data bases of histopathological imagery via the Internet, by investigators working in Europe, North America, and South America. MATERIALS: Experiences derived from medium power (sampling density 2.4 pixels/microm) and high power (6 pixels/microm) imagery of prostatic tissues, skin shave biopsies, breast lesions, endometrial sections, and colonic lesions. Most of the data included in this paper were from prostate. In particular, 1168 histological images of normal prostate, high grade prostatic intraepithelial neoplasia (PIN), and prostate cancer (PCa) were recorded, archived in an image format developed at the Optical Sciences Center (OSC), University of Arizona, and transmitted to Ancona, Italy, as JPEG (joint photographic experts group) files. Images were downloaded for review using the Internet application FTP (file transfer protocol). The images were then sent from Ancona to other laboratories for additional histopathological review and quantitative analyses. They were viewed using Adobe Photoshop, Paint Shop Pro, and Imaging for Windows. For karyometric analysis full resolution imagery was used, whereas histometric analyses were carried out on JPEG imagery also. RESULTS: The three applications of the telecommunication system were remote histopathological assessment, remote data acquisition, and selection of material. Typical data volumes for each project ranged from 120 megabytes to one gigabyte, and transmission times were usually less than one hour. There were only negligible transmission errors, and no problem in efficient communication, although real time communication was an exception, because of the time zone differences. As far as the remote histopathological assessment of the prostate was concerned, agreement between the pathologist's electronic diagnosis and the diagnostic label applied to the images by the recording scientist was present in 96.6% of instances. When these images were forwarded to two pathologists, the level of concordance with the reviewing pathologist who originally downloaded the files from Tucson was as high as 97.2% and 98.0%. Initial results of studies made by researchers belonging to our group but located in others laboratories showed the feasibility of making quantitative analysis on the same images. CONCLUSIONS: These experiences show that diagnostic teleconsultation and quantitative image analyses via the Internet are not only feasible, but practical, and allow a close collaboration between researchers widely separated by geographical distance and analytical resources.

Computers↗

PubMed2001

Apoptosis and cell-cycle regulatory proteins in colorectal carcinoma: relationship to tumour stage and patient survival.

The quantitative assessment of apoptotic index (AI) and mitotic index (MI) and the immunoreactivity of p53, bcl-2, p21, and mdm2 were examined in tumour and adjacent normal tissue samples from 30 patients with colonic and 22 with rectal adenocarcinoma. Individual features and combined profiles were correlated with clinicopathological parameters and patient survival data to assess their prognostic value. Increased AI was significantly associated with increased bcl-2 expression (p<0.008) and the immunoprofiles that included bcl-2, but not with MI, p53, p21 or mdm2. AI was significantly associated with increased Dukes' stage from A, B to C (p<0.02) but not D, while MI showed a significant association with all Dukes' stages (p<0.05). No significant association was found between either AI or MI and prognosis. p53, p21, mdm2, and bcl-2 positivity were detected in 65.4%, 53.8%, 65.4%, and 34.6% of cases, respectively. mdm2 was significantly associated with p53 (p<0.03) and p21 (p<0.04) expression and p53 immunoreactivity was more prevalent in rectal tumours (p<0.008). In univariate survival analysis, bcl-2 overexpression was associated with more favourable patient survival (p<0.03). Positive combined patterns p53+/p21+/bcl-2+ and p21+/mdm2+/bcl-2+ (p<0.005); p53+/bcl-2+, p21+/bcl-2+, and mdm2+/bcl-2+ (p<0.01); and p53+/p21+ (p<0.02) were also associated with favourable clinical outcome. In multivariate Cox survival analysis, bcl-2 (p<0.016) and Dukes' stage (p<0.0001) were the only significant independent prognostic indicators. In conclusion, bcl-2 immunoreactivity was associated with apoptosis and could be used in combination with Dukes' stage as a means of predicting prognosis in colorectal cancer.

Adenocarcinoma↗

PubMed2001

Antisense Bcl-2 oligonucleotide uptake in human transitional cell carcinoma.

OBJECTIVES: Antisense oligonucleotides (AO) downregulate Bcl-2 protein expression in various tumours if good target cell uptake is achieved. In this study, uptake of FITC labelled AO (FITC-AO) directed at Bcl-2 was examined in: (1) the RT4 bladder tumour cell line; (2) normal pig urothelium, and (3) human superficial bladder tumours. METHODS: In the RT4 cell line, uptake of FITC-AO, FITC-scrambled and FITC-sense oligonucleotides were quantified by flow cytometry at 4-hour intervals over 24 h. Uptake of FITC-AO was assessed in normal pig urothelium by flow cytometry after FITC-AO was infused for 1 h. Uptake of FITC AO was assessed in samples from 14 human superficial bladder tumours which were maintained in an ex vivo model. In samples from 6 tumours, uptake at 4 h was assessed using fluorescence microscopy. In samples from 8 separate tumours uptake every 4 h within the first 24-hour incubation period was assessed by flow cytometry. RESULTS: In the RT4 cell line the FITC-AO, FITC-scrambled and FITC-sense oligonucleotide uptake was similar. Disaggregated cells from the normal urothelium of the 3 pigs exhibited 33, 46 and 51% of cells staining positively for FITC-AO as determined by flow cytometry. All 6 tumour samples had detectable intracellular FITC-AO by fluorescence microscopy at 4 h. In the 8 tumours examined over the 24-hour incubation period, there was a range of percentages of positively staining cells. However, most tumours had a monotonic increase in intracellular fluorescence intensity that plateaued 16 h post-infusion. CONCLUSION: Antisense Bcl-2 oligonucleotides were readily taken up by superficial bladder cancer cells but the heterogeneous uptake in tumour samples needs to be considered when assessing the bioavailability of these drugs.

Animals↗

PubMed2001

On prognostic models, artificial intelligence and censored observations.

The development of prognostic models for assisting medical practitioners with decision making is not a trivial task. Models need to possess a number of desirable characteristics and few, if any, current modelling approaches based on statistical or artificial intelligence can produce models that display all these characteristics. The inability of modelling techniques to provide truly useful models has led to interest in these models being purely academic in nature. This in turn has resulted in only a very small percentage of models that have been developed being deployed in practice. On the other hand, new modelling paradigms are being proposed continuously within the machine learning and statistical community and claims, often based on inadequate evaluation, being made on their superiority over traditional modelling methods. We believe that for new modelling approaches to deliver true net benefits over traditional techniques, an evaluation centric approach to their development is essential. In this paper we present such an evaluation centric approach to developing extensions to the basic k-nearest neighbour (k-NN) paradigm. We use standard statistical techniques to enhance the distance metric used and a framework based on evidence theory to obtain a prediction for the target example from the outcome of the retrieved exemplars. We refer to this new k-NN algorithm as Censored k-NN (Ck-NN). This reflects the enhancements made to k-NN that are aimed at providing a means for handling censored observations within k-NN.

Algorithms↗

PubMed2001

Multimegapixel images in histopathology.

OBJECTIVE: To describe methods and procedures for the assembly of very large scale microscopic image arrays. STUDY DESIGN: Microscopic imagery was recorded on different video microphotometers, equipped either with a three-chip CCD Sony MD 760 (Park-ridge, New Jersey, U.S.A.), a COHU vidicon (San Diego, California, U.S.A.) or a PROGRES camera (JenOptik, Jena, Germany), yielding image tiles of 512 x 470, 512 x 470 or 1,496 x 1,120 pixels, respectively. The slide was moved while mounted on a Maerzheuser scanning stage with 0.1-micron precision, under computer control. The MERGE software. (Optical Sciences Center, University of Arizona, Tucson, Arizona, U.S.A.) was written in C and currently implemented on a Sun. Ultra Sparc 2 computer (Sun Microsystems, Palo Alto, California, U.S.A.). RESULTS: The MERGE program allows the assembly of very large scale digitized image arrays preserving exact tile alignment such that even within a single nucleus, highly precise registration is maintained. Images up to 150 megapixels have been assembled, although most practical applications required assembly of only 60-300 tiles. CONCLUSION: The single limiting effect of assembling very large image arrays is the problem of angular misalignment between CCD scan line orientation and scanning stage travel direction. For misalignment of even less than 1 degree, very large arrays need substantial tile overlap. For object areas extending over only 5-10 mm, the effects can be controlled.

Computers↗

PubMed2000

Data representation and reduction for chromatin texture in nuclei from premalignant prostatic, esophageal, and colonic lesions.

BACKGROUND: To identify nuclei and lesions with great specificity, a large set of karyometric features is arranged in the form of a linear profile, called a nuclear signature. The karyometric feature values are normalized as z-values. Their ordering along the profile axis is arbitrary but consistent. The profile of the nuclear signature is distinctive; it can be characterized by a new set of variables called contour features. A number of data reduction methods are introduced and their performance is compared with that of the karyometric features in the classification of prostatic, colonic, and esophageal lesions. METHODS: Contour characteristics were reduced to descriptive statistics of the set of z-values in the nuclear signature and to sequence information. The contour features derived were (1) relative frequencies of occurrence of z-values and of their differences and (2) co-occurrence statistics, run lengths of z-values, and statistics of higher-order dependencies. Performance was evaluated by comparing classification scores of diagnostic groups. RESULTS: Rates for correct classification by karyometric features alone and contour features alone indicate equivalent performance. Classification by a combined set of features led to an increase in correct classification. CONCLUSIONS: Image analysis and subsequent data reduction of nuclear signatures of contour features is a novel method, providing quantitative information that may lead to an effective identification of nuclei and lesions.

Cell Nucleus↗

PubMed2000

An automated machine vision system for the histological grading of cervical intraepithelial neoplasia (CIN).

The histological grading of cervical intraepithelial neoplasia (CIN) remains subjective, resulting in inter- and intra-observer variation and poor reproducibility in the grading of cervical lesions. This study has attempted to develop an objective grading system using automated machine vision. The architectural features of cervical squamous epithelium are quantitatively analysed using a combination of computerized digital image processing and Delaunay triangulation analysis; 230 images digitally captured from cases previously classified by a gynaecological pathologist included normal cervical squamous epithelium (n=30), koilocytosis (n=46), CIN 1 (n=52), CIN 2 (n=56), and CIN 3 (n=46). Intra- and inter-observer variation had kappa values of 0.502 and 0.415, respectively. A machine vision system was developed in KS400 macro programming language to segment and mark the centres of all nuclei within the epithelium. By object-oriented analysis of image components, the positional information of nuclei was used to construct a Delaunay triangulation mesh. Each mesh was analysed to compute triangle dimensions including the mean triangle area, the mean triangle edge length, and the number of triangles per unit area, giving an individual quantitative profile of measurements for each case. Discriminant analysis of the geometric data revealed the significant discriminatory variables from which a classification score was derived. The scoring system distinguished between normal and CIN 3 in 98.7% of cases and between koilocytosis and CIN 1 in 76.5% of cases, but only 62.3% of the CIN cases were classified into the correct group, with the CIN 2 group showing the highest rate of misclassification. Graphical plots of triangulation data demonstrated the continuum of morphological change from normal squamous epithelium to the highest grade of CIN, with overlapping of the groups originally defined by the pathologists. This study shows that automated location of nuclei in cervical biopsies using computerized image analysis is possible. Analysis of positional information enables quantitative evaluation of architectural features in CIN using Delaunay triangulation meshes, which is effective in the objective classification of CIN. This demonstrates the future potential of automated machine vision systems in diagnostic histopathology.

Female↗

PubMed2000

Induction of apoptosis by mitomycin-C in an ex vivo model of bladder cancer.

OBJECTIVE: To examine mitomycin-C (MMC)-induced apoptosis in an ex vivo model of superficial TCC, and relate it to the in vivo response to chemotherapy. Materials and methods Dose- and time-response curves were constructed to determine the optimal conditions for the induction of apoptosis by MMC in an ex vivo model of superficial bladder cancer. Subsequently, 41 individual tumours were exposed to MMC in the model and the effects assessed by measuring of apoptosis before and after chemotherapy. The relationships between tumour grade and stage and the intrinsic and induced apoptotic counts were determined. In tandem, in a clinical study, the relationship between in vivo response of a marker tumour to MMC and the ex vivo induction of apoptosis was determined. RESULTS: In the ex vivo model, apoptosis was induced at a MMC concentration of 0.5 mg/mL after an incubation time of 8 h. In 41 tumours the intrinsic apoptotic index (AI) was higher with increased grade and stage of tumour (P = 0.048). There was no correlation between the intrinsic AI and the AI after treatment with MMC (induced AI). In 21 tumours (51%) the induced AI did not increase above a predetermined response threshold and these tumours were considered resistant to MMC. Resistance to MMC was related to tumour grade (P = 0.037) with a trend for G3 pT1 tumours to be resistant to the therapy. There was a significant association between ex vivo sensitivity and in vivo marker tumour response (P = 0.02). CONCLUSIONS: Apoptosis is differentially induced in an ex vivo incubation model of superficial TCC by MMC and evidence suggests that this response matches that seen in vivo. The measurement of apoptosis before therapy does not predict the apoptotic response of a tumour to chemotherapy. The ability to undergo apoptosis correlates with clinical outcome.

Antibiotics, Antineoplastic↗

PubMed1999

Inference network-based analyses of the histopathological effects of androgen deprivation on prostate cancer.

The evaluation of prostate cancer histology following hormonal therapy often represents a diagnostic problem for the pathologist. Previous studies have shown that an inference or Bayesian belief network (BBN) offers a descriptive classifier useful for the accurate analysis of morphological changes in individual cases of prostate neoplasia. Three different BBNs were evaluated in 94 cancer foci present in 20 radical prostatectomy (RP) specimens and in the matching biopsies in which the initial diagnosis of prostatic adenocarcinoma was made. Ten RP specimens were from patients treated with total androgen ablation or combination endocrine therapy (CET) before surgery. The first and second BBN allowed the identification with high certainty of the cancer foci present in the biopsies and RP specimens, as well as their Gleason grade, the belief value often being close to 1.0. The results of the second BBN showed a good correspondence between the Gleason grade given in the biopsies and that in the RP specimens, except in the surgical material of the treated patients, in which upgrading was always present. The third BBN showed the existence of three subgroups in treated RP specimens, one with morphological effect, another with poor effect, and the third with the histology of untreated (i.e. unaffected) cancer. In conclusion, an inference network-based analysis allows the characterization of treated prostate cancers according to the degree of histopathological change.

Adenocarcinoma↗

PubMed1999

Epithelial tumours of the adult kidney.

The epithelial tumours of the adult kidney, in particular renal cell carcinoma (RCC), are a variety of neoplasms that can be classified by morphology and genotype. Although most are well characterised, typical and less typical tumour variants are recognised. There is evidence to indicate that stage is one of the most important prognostic factors, irrespective of tumour subtype. However, the appropriate handling of nephrectomy specimens is essential for accurate evaluation of diagnostic and prognostic factors in RCC. The problem of how to achieve more objective nuclear grading is still unresolved. The use of diagnostic decision support systems offers the possibility of a flexible approach to this problem, while still utilising morphological criteria. The histopathological analysis remains important, but new techniques of molecular and cell biology will be providing new tools of extraordinary power to sharpen the diagnosis and give it a biological interpretation.

Adult↗

PubMed1999

Interphase cytogenetics of chromosomes 11 and 17 in fine needle aspirates of breast cancer.

The aims of this investigation were to compare quantitative with qualitative analysis of fluorescent in situ hybridization (FISH) centromere signals in interphase breast cancer cell nuclei and to evaluate the possible clinical utility of detecting numerical abnormalities of chromosomes 11 and 17 by FISH in the preoperative prediction of breast cancer histological grade. Commercial digoxigenin-labeled centromere probes to chromosomes 11 and 17 were hybridized to 69 malignant aspirates with histological follow-up. Aspirates were categorized as disomic or aneusomic for chromosomes 11 and 17 qualitatively; a subset of aspirates was also analyzed quantitatively. The quantitative and qualitative approaches resulted in almost identical categorisation. There was a significant association between the qualitative categorization of aspirates as aneusomic or disomic, the histological grade of the excised tumours (P = .0695, n = 69), and the cytological grade of the clinical aspirates (P = .006, n = 35). Although histological grade III tumors were almost invariably polysomic for one or both chromosomes, polysomy was also detected in grade I and II tumors. Qualitative FISH analysis was shown to be more sensitive than cytological grading in predicting histological grade III but was of lower specificity and was therefore not clinically useful.

Adult↗

PubMed1999

An evaluation of intelligent prognostic systems for colorectal cancer.

In this paper we describe attempts at building a robust model for predicting the length of survival of patients with colorectal cancer. The aim of the research, reported in this paper, is to study the effective utilisation of artificial intelligence techniques in the medical domain. We suggest that an important research objective of proponents of intelligent prognostic systems must be to evaluate the additionality that AI techniques can bring to an already well-established field of medical prognosis. Towards this end, we compare a number of different AI techniques that lend themselves to the task of predicting survival in colorectal cancer patients. We describe the pros and cons of each of these methods using the usual metrics of accuracy and perspicuity. We then present the notion of intelligent hybrid systems and evaluate the role that they may potentially play in developing robust prognostic models. In particular we evaluate a hybrid system that utilises the k Nearest Neighbour technique in conjunction with Genetic Algorithms. We describe a number of innovations used within this hybrid paradigm used to build the prognostic model. We discuss the issue of censored patients and how this issue can be tackled within the various models used. In keeping with our objective of studying the additionality that AI techniques bring to building prognostic models, we use Cox's regression as a standard and compare each AI technique with it, attempting to discover their capabilities in enhancing prognostic methods in medicine. In doing so we address two main questions--which model fits the data best?, and are the results obtained by the various AI techniques significantly different from those of Cox's regression? We conclude this paper by discussing future enhancements to the work presented and lessons learned from the study to date.

Age Factors↗

PubMed1999

High metallothionein expression is associated with features predictive of aggressive behaviour in endometrial carcinoma.

AIMS: Metallothioneins (MTs) are a group of ubiquitous low molecular weight proteins with a high affinity for heavy metal ions. The aim of the present study was to investigate MT expression in a series of endometrial carcinomas. We wished to determine whether MT expression in endometrial carcinoma was related to established prognostic factors such as tumour grade, stage and histological type. We also wanted to establish if high MT expression in curettings of endometrial carcinoma was predictive of high expression in the subsequent hysterectomy specimen. METHODS AND RESULTS: Sixty-three cases of endometrial carcinoma were included in the study. These comprised 57 endometrioid adenocarcinomas (15 grade 1, 25 grade 2, 17 grade 3), three papillary serous adenocarcinomas, two mucinous adenocarcinomas and one clear cell adenocarcinoma. Forty-five tumours were stage I, 10 were stage II and eight were stage III. In 28 cases, diagnostic endometrial curettings, performed prior to hysterectomy, were available for study. Immunohistochemical staining was performed using the anti-MT monoclonal antibody E9. The intensity and distribution of MT staining were assessed using a semiquantitative method. This resulted in an intensity distribution (ID) score out of a maximum of 300. The mean ID score of grade 1 and 2 endometrioid adenocarcinomas was 67 and 63, respectively, while for grade 3 tumours the mean ID score was 114. This was statistically significant (P = 0.05). The three papillary serous adenocarcinomas had high ID scores with a mean of 208. The mean ID score of stage I tumours was 69. This was lower than those of stage II and III tumours which had mean ID scores of 116 and 128, respectively. However, these differences were not statistically significant (P = 0.288). A significant correlation was observed between MT ID scores in endometrial curettings and in the subsequent hysterectomy (P = 0.013). CONCLUSIONS: MT isoforms can be demonstrated in most endometrial adenocarcinomas. High MT ID scores are associated with high grade and high stage endometrial adenocarcinomas and with the aggressive papillary serous adenocarcinoma. Whether this is of value as an independent prognostic factor has yet to be established.

Adenocarcinoma↗