Steepness of dose-response curve for larynx cancer.
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Dose-Response Relationship, Radiation↗
Biomedical subjects
R Chappell
Publications and source records attributed to R Chappell.
Local control versus dose or overall time: from coefficients to percentages.
When clinical results are analysed to find the treatment variables which affect the outcome, two types of multivariate analysis are done. Firstly, a determination of which variables are important is made: from age, gender, stage, histology, total dose, overall time, etc. Secondly, a quasi-biological model may be set up which includes those variables, e.g. Function (p) = Variable 1 + Variable 2 + ... + alpha x dose + beta x dose x (dose per fraction) - gamma x (overall time) where p is the probability of local control and "Function" is a logit or double-log function. The coefficients thus determined are often presented simply in raw form, or as ratios such as alpha/beta or gamma/alpha where any conversion factors from "Function (p)" to percentages are assumed conveniently to cancel out. However, it is mathematically possible to convert each coefficient directly into "percent change in local control per unit dose" (for alpha), or "percent per unit time" (for gamma), without recourse to the obvious convenience of the ratios. These converted values are more understandable than the coefficients themselves. They mean the rate of change of local control with (for example) total dose if overall time and dose per fraction were held constant; or rate of loss of local control with prolongation if total dose and dose per fraction were held constant. Even though heterogeneity may alter these slopes considerably from the theoretically maximum Poisson slopes, they still tell us what is happening averaged over the group of patients being studied, with often interesting insights.
Dose-Response Relationship, Radiation↗
Analysis of clinicopathologic prognostic features in patients with gastric adenocarcinoma.
BACKGROUND: We evaluated the influence of several clinicopathologic variables on 5-year actuarial survival rate after curative resection of gastric adenocarcinoma. METHODS: Clinical characteristics were retrieved from the records of all patients who underwent gastric resection for curative intent between 1965 and 1986 at The University of Chicago Medical Center, and follow-up was obtained from our tumor registry. Pathologic characteristics were determined from a detailed review of all available histopathologic slides. RESULTS: One hundred seventy-eight patients underwent a curative resection during the study period at our institution. Overall 5-year actuarial survival rate was 29%. The relationship between clinicopathologic variables and 5-year survival rate was evaluated by Kaplan-Meier survival curve construction and chi-squared analysis. Lymphatic and/or capillary microinvasion (absent vs present, p < 0.001), tumor location (antrum and body vs gastroesophageal junction, p = 0.05), local extent of disease (limited to the gastric wall versus involving adjacent organs, p = 0.003), stage (absence versus presence of lymph node metastases, p < 0.001), Lauren type (intestinal versus diffuse, p < 0.01), and Ming type (expanding versus infiltrative, p < 0.02) significantly influenced survival. When a multivariate analysis with logistic regression of 5-year survival was performed, lymphatic and/or capillary microinvasion emerged as the only statistically significant, independent prognostic factor associated with long-term survival (p = 0.039). If microinvasion was omitted from the analysis, lymph node metastases (p < 0.05) and the extension to adjacent organs (p < 0.04) became the only statistically significant variables. Multiple correlation analyses suggested that microinvasion is an early histopathologic finding that correlates with a more aggressive natural history. CONCLUSIONS: Lymphatic and/or capillary microinvasion is a more powerful predictor of 5-year survival than lymph node metastases or tumor extension to adjacent organs. Correlation among clinicopathologic variables suggests that microinvasion may represent an early finding, serving as a potential marker for a biologically more aggressive tumor.
Adenocarcinoma↗
Effect of overall time and dose on the response of glottic carcinoma of the larynx to radiotherapy.
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Glottis↗
The Goldilocks dilemma in survey design and its solution.
A dilemma appears in the design of any survey with followups intended to detect the occurrence of an event. Suppose that, at followup, the event of interest can only be determined to have occurred since the previous interview (such is often the case, for example, with onset of dependent behavior in the aged). Then a followup which takes place too soon runs the risk of observing no or very few events, while a followup which is conducted after too long a wait might observe events in nearly every subject, and so be equally uninformative. Thus we would have what one investigator compares to Goldilocks dilemma: is the interval before followup too short, too long, or just right? The problem is multiplied when more than one followup is intended. As a partial solution, a technique is described here which provides guidance on the spacing of followup waves in a multiwave study, preventing possibly serious inefficiencies in study design. Data from the Massachusetts Health Care Panel Study (MHCPS) on functional dependence in the elderly are used for a demonstration.
Data Collection↗
The relationship between marital breakdown and childbearing in England and Wales.
"The paper uses data on women from the General Household Surveys for 1986-89 [for England and Wales] to form combined multiple decrement tables on the transitions from first marriage through childbearing, divorce and remarriage. It shows that ultimately women who experience one marital breakdown tend to have around the same number of children...as those who remain married. However, their time to complete childbearing is rather longer with this extra time being concentrated largely in the birth interval in which the marital breakdown takes place. The group of women who experience more than one marital breakdown tend to have more children and consequently shorter birth intervals."
Birth Intervals↗
Comparison of the physical properties of two types of polydimethyl siloxane for fabrication of facial prostheses.
The in vitro physical properties of two types of polydimethyl siloxane, MDX 4-4210 and a new material A-2186, were compared. The properties that were investigated in this study were tensile strength, elongation, tear strength, and surface hardness. The properties tested were selected because of their clinical significance for fabricating a facial prosthesis. According to the results obtained in this investigation, the new material, A-2186, had greater tear resistance, tensile strength, and a larger percentage of elongation. A-2186 material, also proved to be softer at the surface than the MDX 4-4210. This combination of physical properties makes this material, A-2186, a better choice than the traditional MDX 4-4210 for the fabrication of facial prostheses.
Biocompatible Materials↗
Sampling design of multiwave studies with an application to the Massachusetts Health Care Panel Study.
A technique is presented which provides guidance on the spacing of follow-up waves in a multiwave study. Only information from the baseline wave is needed, as well as rough parameter estimates for the survival distribution. The computations use the expected Fisher information; a new method for its calculation is given. An analysis of the effects of simplifying assumptions, such as presuming that a distributional parameter is known, shows that gross discrepancies may result. Data from the Massachusetts Health Care Panel Study (MHCPS) are used for a demonstration. The MHCPS example shows that this technique can prevent large inefficiencies in multiwave experimental design.
Activities of Daily Living↗
Verification of a new clinicopathologic staging system for colorectal adenocarcinoma.
Rectal adenocarcinoma is said to have a poorer outcome than colon adenocarcinoma when compared on the basis of Dukes' staging. However a new staging system, determined by a multivariate analysis of 147 patients with rectal adenocarcinoma, has revealed three other variables significantly related to outcome. Therefore this study analyzed the authors' experience with colonic carcinoma during the same time period as they had studied for rectal carcinoma to determine whether the new staging system is valid for colon carcinoma as well, and, if so, to compare the outcome of patients with colon and rectal carcinoma on the basis of this new staging. A total of 603 patients with 611 colonic adenocarcinoma were operated on at the University of Chicago Medical Center between 1965 and 1981. Two hundred seventy-nine adenocarcinomas (45.7%) were located proximal to the splenic flexure and 332 (54.3%) were located between the splenic flexure and the rectosigmoid. Four hundred sixty-two patients underwent segmental colectomy, 46 subtotal colectomy, 26 total colectomy, 18 proctocolectomy, 5 abdominal-perineal resection, 1 appendectomy, while 20 had local excision of the tumor through colotomy and 25 had permanent diverting stoma as the only procedure. The operative mortality rate was 6.1% in the whole group, but was only 2.7% in the group of potentially curable patients. Complete follow-up was obtained in all patients. To validate a previous staging system for Dukes' B and C rectal adenocarcinoma, the authors investigated the correlation between 5-year survival for colonic carcinoma patients and all relevant variables that they had considered potentially meaningful in the previous study with rectal adenocarcinoma. The resulting multivariate analysis using Cox regression showed that the four variables found previously to be significantly related to outcome for rectal adenocarcinoma patients (stage, race, tumor morphology, and vascular and/or lymphatic microinvasion) were the only four variables significantly (p less than 0.05) associated with outcome for colonic adenocarcinoma patients. In addition, by using the results of their previous staging system for rectal adenocarcinoma patients, they 'predicted' the 5-year survival rates of the colon adenocarcinoma patients, divided in 16 staging subgroups. In subgroups of at least 15 patients, the rectal staging system predicted the outcome to within 1 to 6 percentage points of the observed outcome of the colonic adenocarcinoma patients. Thus this study validates this staging system, incorporating stage, race, tumor morphology, and microinvasion to predict 5-year survival rate more accurately than Dukes' staging alone for both colon and rectal adenocarcinoma.(ABSTRACT TRUNCATED AT 400 WORDS)
Academic Medical Centers↗
Primary and recurrent Crohn's disease. Experience with 1379 patients.
Between 1970 and 1988, 1379 patients with Crohn's disease were treated at the University of Chicago. Of these, 639 (mean age, 32.5 years; 322 men, 317 women) required at least one surgical procedure. The most common indications for operation were failure of medical treatment (n = 215, 33%), presence of a fistula (n = 154, 24%), and bowel obstruction (n = 141, 22%). A fistula was the most common intraoperative Crohn's-related complication. In 582 patients (92%), a resection was necessary, with primary anastomosis in 416 (65%), a temporary stoma in 124 (20%), and a permanent stoma in 42 (7%). The remaining 57 patients underwent diverse procedures (stricturoplasty, bypass, and so on). Two patients (0.3%) died. Follow-up data was obtained in 95%. One hundred eighteen patients developed recurrence requiring reoperation. The recurrence rate was 20% at 5 years and 34% at 10 years. The recurrence involved a permanent stoma or a previous anastomosis in 62 patients (afferent limb in 46, efferent in 16). In the 391 patients without previous surgery for Crohn's disease, a covariate analysis was performed to determine those variables significantly associated with recurrence. Variables included demographic data, findings at operation, surgical procedures, and histopathologic characteristics. The analysis revealed that the number of sites involved was the only variable that was significantly associated with the intra-abdominal recurrence rate (p less than 0.001). The annualized risk of recurrence was 1.6% for patients with single-site involvement and 4% for those with multiple-site involvement. Perineal disease was associated with a significantly higher risk of local recurrence than any other site (p less than 0.02). A subanalysis of 236 patients with single-site involvement but no previous operation allowed us to study the influence of site on indications for surgery and type of operative procedure. Failure of medical treatment was the most common indication for all sites. In contrast the site involved influenced the procedure: resection and primary anastomosis was feasible in 88% of jejunoileal and terminal ileal cases and a temporary ileostomy was necessary in only 12%. No patients with small bowel localization required a permanent stoma. A resection with primary anastomosis was feasible in only 32% of patients with colonic disease. The remaining two thirds of patients required either a temporary or a permanent stoma. It is concluded that multisite involvement is associated with 2.5 times the rate of recurrence of single-site disease, while the presence of perineal disease has a significantly higher incidence of local recurrence.(ABSTRACT TRUNCATED AT 400 WORDS)
Adult↗
Fitting bent lines to data, with applications to allometry.
Change-point models, in which a linear or non-linear relation is generalized by allowing it to change at a point not fixed in advance, are of growing importance in allometric and other types of modeling. Frequently, the change-point is picked "by eye" and separate regressions are run for each resultant subdomain. This procedure is deficient, however, for the following reasons: first, a repeatable and objective procedure for estimating the change-point has not been used; second, the subsequent analysis usually does not take into account the fact that the change-point is estimated from the data; and last, the usually desirable requirement of continuity at the change-point is ignored. This paper describes various methods for jointly estimating linear relations and the intervening change-point from the data. In the simplest case, with normal errors and a linear relation of one variable upon another, this amounts to fitting a "bent line" via least squares techniques. In addition, tests and graphical diagnostics for the presence of change-points are presented. An example is given where a change-point and slopes are estimated for the relation of running speed with size among land mammals. In the past, these data have been fit with a straight line or a parabola. It is shown here that superior fit and interpretability are achieved using a change-point model.
Animals↗
Ras oncogene expression as a prognostic indicator in rectal adenocarcinoma.
In order to investigate the value of ras oncogene expression as a prognostic indicator in rectal adenocarcinoma, we evaluated the level of ras gene protein product (p21) in the available material of 149 consecutive Dukes' B and C specimens resected at our institution between 1965 and 1981. Five year follow-up was available in all patients. Pathology slides and archival paraffin blocks were retrieved for confirmation of the original diagnosis, study of histopathological features, and measurement of p21 content. P21 titers were obtained using the RAP-5 monoclonal antibody in a semiquantitative immunohistochemical assay. Titer was expressed as the highest dilution of antibody giving definitive staining using the avidin-biotin peroxidase method. The analysis indicated that the group of tumors with high (greater than or equal to 1:40,000) p21 titers had a worse 5-year survival (43.9 versus 64.3%, P less than 0.02), higher incidence of distant metastases (51.8 versus 23.2%, P less than 0.001), and more advanced Dukes' stage (53.7 versus 35.7% incidence of Dukes' C stage, P less than 0.04) than tumors with low (less than 1:40,000) titers. Multivariate analysis also demonstrated that the influence of the level of ras gene protein product on survival was independent of Dukes' stage. We conclude that detection of high levels of ras oncogene protein product indicates a group of tumors with a more aggressive behavior, characterized by a higher percentage of distant recurrences and worse prognosis. These findings suggest that measurement of p21 may become clinically important in identifying patients at high risk of recurrent disease.
Adenocarcinoma↗
A 5- to 21-year follow-up and analysis of 250 patients with rectal adenocarcinoma.
A total of 250 patients with rectal adenocarcinoma were operated on at the University of Chicago Medical Center between 1965 and 1981. The operation performed was curative resection in 154 patients, palliative resection in 16 patients, diverting colostomy in 21 patients, exploratory laparotomy in 11 patients, and transanal removal in 48 patients. Of the 154 curative resections, 115 were abdomino-perineal (APR), three were total proctocolectomies, and 36 were low anterior resections (LAR). No anastomotic complications were observed in this latter group. Operative mortality was 3%. Complete follow-up was obtained in 152 patients (98.7%). Five- and 10-year actuarial survival rates were 68.8 and 59.4%, respectively, for patients with Dukes' B1 adenocarcinoma (n = 32), 55.8 and 44.2% for Dukes' B2 tumors (n = 52), and 42.9% and 25.4% for Dukes' C tumors (n = 63). Distant metastases developed in 59 patients (39.6%), and pelvic recurrence developed in another 18 patients (12%); 5-year survival rates were 23.6% and 22.2%, respectively. Multivariate analysis with Cox regression showed that stage (p = 0.0001), race (p = 0.03), tumor morphology (p = 0.02), and vascular and/or lymphatic microinvasion (p = 0.001) were statistically significant in their association with survival. Logistic regression analysis confirmed these results and allowed for the estimation of 5-year survival probabilities in 16 groups of patients defined by various associations of these four factors. These estimates ranged from a high of 92% in Caucasian patients with Stage B, exophytic tumors with no vascular or lymphatic microinvasion, to a low of 14% in black patients with Stage C, nonexophytic tumors and with the presence of vascular and/or lymphatic microinvasion. Univariate analysis showed that histologic type (p = 0.0006), stage (p = 0.05) and vascular and/or lymphatic microinvasion (p less than 0.001) were significantly associated with the incidence of pelvic recurrence. Analysis of the extent of the operation revealed that the incidence of pelvic recurrence was reduced by the performance of a wide pelvic lymphadenectomy (9.4% vs. 16.4%), but the result did not reach statistical significance (p = 0.16). In conclusion, this study confirms the well-established prognostic value of the Dukes' staging classification of rectal carcinoma. Further, the analysis reveals that race, tumor morphology, and the presence or absence of lymphatic and/or vascular microinvasion significantly influence outcome. By associating these four statistically significant and independent variables, the prognosis for any individual patient can be estimated more precisely than by using Dukes' staging alone.(ABSTRACT TRUNCATED AT 400 WORDS)
Adenocarcinoma↗
Importance of tumor morphology for the long term prognosis of rectal adenocarcinoma.
A retrospective review of 149 consecutive potentially curable rectal adenocarcinomas operated on at our institution between 1965 and 1981 was carried out to assess whether tumor morphology influences long term survival. Complete follow-up was available on all patients and extended to 20 years. Data on tumor morphology was extracted from pathology reports and was available in 147 cases (98.6%). Tumors were defined as exophytic (n = 76) when exhibiting a polypoid growth pattern protruding into the lumen at least 1 cm; when lacking such characteristic growth pattern, tumors were classified under the general term of nonexophytic (n = 71). The 5 year survival rate calculated with life table analysis was 80 per cent for exophytic carcinomas and 54.1 per cent for nonexophytic tumors. This difference was verified by logistic regression analysis and proportional hazard technique and is statistically highly significant (P = 0.001). The rate of distant metastases was 29.7 per cent for exophytic adenocarcinoma and 48.6 per cent for nonexophytic tumors (P = 0.02). Although the results did not reach statistical significance, local recurrence of tumor occurred about twice as often in nonexophytic tumors (15.7%) compared with exophytic tumors (8.1%). Thus, we conclude that tumor morphology is an important preoperative prognostic factor for survival and prediction of distant metastasis, and possibly for local recurrence.
Actuarial Analysis↗
Human chorionic gonadotrophin expression in colorectal adenocarcinoma.
The presence of human chorionic gonadotrophin (HCG) in colorectal adenocarcinoma was studied histologically in 45 tumors using immunoperoxidase technique. Ten neoplasms (22.2 percent) contained HCG-positive tumor cells. These cells were present mostly at the periphery of the tumors. Many formed parts of glands, while some were arranged in syncytial clumps or columns, or singularly. Thus, these tumor cells resembled trophoblastic tissue not only in being HCG-positive but also in their peripheral distribution and occasionally in morphologic appearance. HCG-positive tumors were seen more commonly in the rectosigmoid region (90 percent) and were more aggressive than HCG-negative tumors. In this study, lymph node or liver metastases were present in 70 percent of HCG-positive tumors compared with 29 percent of negative tumors--a difference which is statistically significant.
Adenocarcinoma↗
Exfoliative dermatitis: presenting sign of internal malignancy.
Exfoliative dermatitis is most commonly associated with antecedent cutaneous disorders, medications, and lymphoreticular malignancies. Three patients with exfoliative dermatitis associated with internal carcinoma are described. The importance of thorough evaluation of all patients who present with exfoliative dermatitis is stressed.
Adenocarcinoma↗
Cardiotoxicity of diazepam in cultured heart cells.
The responses of primary cultures of rat myocardial cells to diazepam (Valium) were evaluated. The cells were exposed to 4, 16 or 32 microgram/ml of diazepam for 1, 4 or 24 h. The cultures were evaluated for changes in beating activity and morphology and for cytotoxic effects. After the 1-h treatment exposure, the cultures exhibited tachycardia which was dose-dependent. The longer durations of treatment either produced arrhythmias or caused a loss of beating. Major morphological alterations observed were the formation pseudopodia and increased cytoplasmic granulation. Cytotoxicity was measured quantitatively by leakage of lactic dehydrogenase (LDH) from the cells into the media and by cell viability. Moderate amounts of LDH were leaked from the cells after exposure to diazepam for 4 h. After 24 h of treatment with the higher concentrations of diazepam, cell viability was greatly reduced.
Animals↗
Gingival health and dental health attitudes in 766 Winnipeg high school students.
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Adolescent↗