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Biomedical subjects

R A Spence

Publications and source records attributed to R A Spence.

At least 37 records · Page 2Linked to original sources

Familial adenomatous polyposis.

Familial adenomatous polyposis (FAP) is an autosomal dominant condition resulting in the development of more than 100 adenomatous polyps in the large bowel. In addition, a number of extracolonic manifestations of the condition may occur. Recently, increasing knowledge relating to the extracolonic abnormalities, and localization and sequencing of the gene for FAP, have had important implications for screening and long-term follow-up of those affected. In this review the natural history of the disease and the extracolonic manifestations associated with it are considered. Surgical management and advances in understanding at a molecular level are discussed, as well as the problems relating to screening for FAP and the implications of the new knowledge.

Adenomatous Polyposis Coli↗

The role of congenital hypertrophy of the retinal pigment epithelium in screening for familial adenomatous polyposis.

Retinal examination by indirect ophthalmoscopy was performed on seventy members from 20 kindreds demonstrating the clinical manifestations of familial adenomatous polyposis and forty controls. Thirty-four of 43 affected patients manifested CHRPE lesions compared with 2 of 27 at risk and 2 of 40 controls giving a sensitivity of 79% and specificity of 95% based on the control group. The difference between the affected and at risk groups was significant (Chi-squared = 34.098, 1 df, P = 0.001). The low sensitivity and variation in incidence of CHRPE in FAP patients and general population documented in the world literature prevent its use as a sole marker for the condition. With advances in knowledge of the disease at a molecular level it is now possible to alter risks for families by DNA analysis. There remain a number of patients in whom such techniques do not significantly alter risks. In these families by combining the results of DNA analysis, sigmoidoscopy and retinal examination it may be possible to alter risks by a significant degree. Retinal examination should be reserved for those families in whom risks cannot be altered sufficiently by DNA analysis alone.

Adenomatous Polyposis Coli↗

Jass' classification revisited.

BACKGROUND: In 1986, Jass and colleagues claimed to have improved on Dukes' classification of prognosis for carcinoma of the colon and rectum. To have clinical relevance, such results should be reproducible and confirmed by other institutions. STUDY DESIGN: Retrospective clinicopathologic study of 312 carcinomas of the colon and rectum to determine whether or not Jass' classification is superior to that of Dukes' as assessed by their relative reproducibility and prognostic significance. RESULTS: Dukes' classification had excellent intraobserver and interobserver reproducibility (kappa values of 0.86 and 0.93, respectively). In contrast, the reproducibility of variables assessed by Jass showed only slight to fair agreement (lymphocytic infiltration: intraobserver and interobserver kappa values of 0.08 and 0.05, respectively, growth pattern: intraobserver and interobserver kappa values of 0.37 and 0.41, respectively). Dukes' stage and patient age were the most important prognostic variables on multivariate regression analysis. Tumor differentiation, nuclear polarity, tubule configuration, and lymphocytic infiltration remained significantly related to survival in the presence of Dukes' stage and age. The model which best predicted prognosis was a combination of Dukes' stage, patient age and tumor differentiation. Further addition of the variables assessed by Jass to this model did not significantly improve the prediction of prognosis. CONCLUSIONS: Dukes' classification is of greater prognostic value and more reproducible than the components of Jass' classification. The continued use of Dukes' classification is, therefore, warranted for prognostic and therapeutic decisions in patients with carcinoma of the colon and rectum.

Colonic Neoplasms↗

Colorectal carcinoma: importance of clinical and pathological factors in survival.

A series of clinicopathological variables was assessed on 312 patients undergoing surgical resection for primary colorectal cancer. Although the presence of venous invasion was related to mortality (P = 0.02), classifying invasion into involvement of thick-walled or thin-walled veins did not produce a variable of prognostic value. Intestinal obstruction (P = 0.04) and the macroscopic appearance of the tumour (P = 0.04) were related to mortality from colorectal cancer, but not from all causes of death. Duke's stage, increasing patient age and poorly differentiated tumours were the variables which were individually most significantly related to poor prognosis (P < 0.001 for each analysis). Cox's regression analysis identified these three variables as independent predictors of outcome in colorectal cancer. This study confirms that Duke's stage, patient age and tumour differentiation are still the most important clinicopathological variables in colorectal cancer.

Adult↗

DNA densitometry of colorectal cancer.

DNA analysis was assessed by densitometry for 281 cases of colorectal adenocarcinoma. Detection of aneuploidy in a single case rose from 65% if one, to 92.5% when three or more sections, were analysed. Although aneuploid tumours had significantly larger nuclear areas than near diploid tumours (p = 0.009), densitometric measurements showed no association with clinicopathological variables. DNA content determined by densitometry was compared with that from flow cytometry on 465 tissue sections from 241 cases. Aneuploidy assessed by flow cytometry was significantly associated with that determined by densitometry (p < 0.01 for all comparisons), ploidy state being similar in 381 sections (82%, kappa = 0.63, p < 0.001), and 187 cases (77.6%, kappa = 0.57, p < 0.001). Univariate survival analysis showed that DNA densitometric variables had no significant association with survival in (a) all cases, (b) cases without lymph node metastases, or (c) cases without distant metastases. Multivariate regression analysis of densitometric and clinicopathological variables identified Dukes's stage, patient age, and tumour differentiation as the combination of variables most closely related to survival. Densitometric measurement of DNA content could not significantly improve on the prognostic model containing these three variables. It is concluded that, although the assessment of DNA content by densitometry is comparable with that of flow cytometry, conventional histological variables remain the best predictors of prognosis in colorectal cancer.

Adenocarcinoma↗

The role of flow cytometry in carcinoma of the colon and rectum.

Flow cytometry was performed upon 312 patients with adenocarcinoma of the colon and rectum, satisfactory results being obtained with 275 (108 diploid, 130 aneuploid and 37 tetraploid). The proportion of nondiploid instances increased from 28 percent if one, to 80 percent when six specimens were assessed per patient. Reproducibility of the technique showed substantial agreement in the assessment of deoxyribonucleic acid ploidy (Kappa value equals 0.74). Increasing values of cells in the diving (G2/M) phase of the cell cycle were associated with little lymphocytic tumor infiltration (p = 0.0002) and extensive tumor fibrosis (p = 0.003). Univariate survival analysis revealed that, although diploid tumors tended to have a better prognosis than nondiploid tumors (p = 0.06), no flow cytometric variable was significantly related to survival. Flow cytometry similarly was not of prognostic value in instances without lymph node metastases or without distant metastases. Multivariate regression analysis of flow cytometric and clinicopathologic variables identified Dukes' stage, patient age and tumor differentiation as the combination of variables most closely related to survival. No flow cytometric variable could significantly improve on the prognostic model containing these three variables. It is concluded that conventional histologic variables remain the best predictors of prognosis in carcinoma of the colon and rectum.

Adenocarcinoma↗

Prognostic factors in colorectal cancer.

The prognostic power of the extent of tumour invasion is indisputable; Dukes' classification has repeatedly been proven to be strongly correlated with patient survival. Modifications have led only to confusion, resulting in caution being required in the classification of patients with Dukes' A tumours. In the UK, the American tumour node metastasis and Australian clinicopathological systems are frequently considered too complex for routine clinical use. Meanwhile, Jass's classification may be complicated by observer variation between pathologists, and recent evidence suggests that it offers no advantage over that of Dukes. All the conventional staging systems also fail to take the skill of the surgeon into account when determining outcome. Attempts at quantifying tumour structure have not heralded the expected major advance. For instance, the expense and uncertain prognostic value of tumour DNA content assessed by flow cytometry are likely to restrict widespread use of this technique. It may soon be possible, however, to provide optimum treatment for patients based on individual tumour doubling times. Classification using knowledge of how a small number of cells in the tumour have the ability to invade locally, enter blood vessels and metastasize would also provide important prognostic information on which treatment could be based. Until then, the ease of use and high prognostic power of Dukes' classification ensure that, after 60 years, it is still the 'gold standard' against which all other prognostic classifications in colorectal cancer should be assessed.

Colorectal Neoplasms↗

An evaluation of radionuclide bone scanning and liver ultrasonography for staging breast cancer.

The use of nuclear bone scanning and liver ultrasonography to stage breast cancer is an established practice in many hospitals. A 3 year prospective study was undertaken to assess the usefulness of these two investigations. Three hundred and fifty-eight patients were analysed: 133 had stage I disease, 188 were stage II and 37 were stage III. Bone scans were performed on 339 (94.7%) patients; 302 had stage I or stage II disease; and 37 were stage III. Bone scans were positive for metastases in only 0.9% of stage I and II patients but were positive in 16.2% of patients with stage III disease. None of the 309 (96.2%) stage I or stage II patients who had an ultrasound scan had any liver metastases detected whereas positive scans were obtained in 5.4% of stage III patients. It can be concluded that the incidence of demonstrable bone or liver metastases in stage I and stage II breast cancer patients is so low that the use of routine scanning can be abandoned.

Adult↗

Solitary thyroid nodule: a prospective evaluation of nuclear scanning and ultrasonography.

The aim of this study was to assess prospectively the value of thyroid nuclear scans and ultrasound examination in the preoperative investigation of patients with a solitary thyroid nodule. Total thyroid lobectomy for a solitary thyroid nodule was performed in 68 cases. Each patient had a thyroid isotope scan (except two women who were pregnant) and thyroid ultrasound examination. There were 10 (15 per cent) malignant nodules, 11 (16 per cent) benign neoplastic nodules and 47 (69 per cent) benign non-neoplastic nodules. All of the patients with malignant nodules who were scanned had a solitary cold nodule on thyroid scan, as did 40 (69 per cent) of those with benign solitary nodules. Ultrasound examination of the thyroid suggested correctly that one of 16 (6 per cent) cystic lesions, four of 16 (25 per cent) complex solid-cystic lesions and three of 18 (17 per cent) of solid lesions were malignant. One lesion reported as multinodular on ultrasonography and one reported as normal also turned out to be malignant. Thyroid isotope scans and ultrasound do not accurately differentiate between benign and malignant conditions and their routine use in the investigation of a solitary thyroid nodule should be abandoned.

Diagnosis, Differential↗

Irresectable hepatoma treated by intrahepatic iodized oil doxorubicin hydrochloride: initial results.

In this study we describe the investigation and treatment of 14 patients with primary hepatocellular carcinoma. Patients were treated with intra-arterial infusion of iodized oil and doxorubicin hydrochloride. Five of these patients were alive after 1 year. Twelve patients showed a fall in alpha-fetoprotein, and in seven of these patients, the fall in alpha-fetoprotein was greater than 50%.

Adult↗

Ascites and serum bilirubin value predict survival in acute variceal bleeding.

Factors affecting the outcome of acute variceal haemorrhage treated by injection sclerotherapy were analysed. The data on 82 patients undergoing their first admission for acute variceal bleeding were collected prospectively. Using multiple logistic regression analysis and multiway contingency table analysis only the presence of ascites and an elevated serum bilirubin value contributed independently to survival out of a total of 26 discontinuous and 12 continuous variables. A derived regression equation was constructed to predict survival using the data from the 82 patients and this was tested against the observed outcome in a different group of 113 patients also undergoing their first variceal haemorrhage treated by injection sclerotherapy, the data from whom were also collected prospectively. Using a cut-off point of P = 0,71, the equation accurately predicted death for 91% of patients who died and accurately predicted survival for 65% of patients who survived. Overall accuracy of prediction was 73%.

Acute Disease↗

Disturbed oesophageal motility after eradication of varices by chronic sclerotherapy--a scintigraphic study.

Oesophageal function after sclerotherapy for varices in 29 patients was compared with that in 15 patients with untreated varices using a scintigraphic technique. The first group had significantly longer transit times in each third and also in total time compared with a control group of 32 subjects (upper-third P = 0,02; middle-third P = 0,01; lower-third P = 0,0001; and total transit time P = 0,0001). Minor abnormalities of transit were found when the untreated group was compared with controls (increased total transit time P = 0,02). These results indicate that abnormalities of transit are increased after sclerotherapy for varices.

Adult↗