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Bone metastasis: review and critical analysis of random allocation trials of local field treatment.

PURPOSE: Compare and contrast reports of random allocation clinical trials of local field radiation therapy of metastases to bone to determine the techniques producing the best results (frequency, magnitude, and duration of benefit), and relate these to the goals of complete relief of pain and prevention of disability for the remaining life of the patient. METHODS AND MATERIALS: Review all published reports of random allocation clinical trials, and perform a systematic analysis of the processes and outcomes of the several trial reports. RESULTS: All trials were performed on selected populations of patients with symptomatic metastases and most studies included widely diverse groups with regard to: (a) site of primary tumor, (b) location, extent, size, and nature of metastases, (c) duration of survival after treatment All trial reports lack sufficient detail for full and complete analysis. Much collected information is not now available for reanalysis and many important data sets were apparently never collected. Several of the variations in patient and tumor characteristics were found to be much more important than treatment dose in the outcome results. Treatment planning and delivery techniques were unsophisticated and probably resulted in a systematic delivery of less than the assigned dose to some metastases. In general the use and benefit of retreatment was greater in those patients who initially received lower doses but the basis and dose of retreatment was not documented. Follow-up of patients was varied with a large proportion of surviving patients lost to follow-up in several studies. The greatest difference in the reports is the method of calculation of results. The applicability of Kaplan-Meier actuarial analysis, censoring the lost and dead patients, as used in studies with loss to follow-up of a large number of patients is questionable. The censoring involved is "informative" (the processes of loss relate to the outcome) and not acceptable since it results in artificial elevation of the frequency of response. Overall, higher dose fractionated treatment regimens produced a better frequency, magnitude, and duration of response than lower dose single-fraction regimens. Relapse after initial response was frequent. The "median duration of relief" was much shorter than the "median duration of survival" post-treatment. Thus the "net pain relief" is far less than the goal of pain relief for the total duration of life after treatment. CONCLUSIONS: The pain relief obtained in all studies is poor and our care practices need to be improved. Many patients never achieved complete relief and for most who did, the duration of relief was much less than their period of survival after treatment. Higher dose, fractionated treatments produced a greater frequency, magnitude, and duration of response with an improved "net pain relief." Additional trials with selection of comparable cases, good definition of extent of disease, exemplary treatment, and complete follow-up are required.

Analgesics↗

Time factors in larynx tumor radiotherapy: lag times and intertumor heterogeneity in clinical datasets from four centers.

PURPOSE: To use the time-dependent linear-quadratic model, both in the standard form and in a form modified to incorporate intertumor heterogeneity, in a reanalysis of 4 datasets for larynx tumor control, to provide more representative and direct estimates of the lag period, the time factor (lambda/alpha), and the clonogen population inactivation dose ([lnk]/alpha). METHODS AND MATERIALS: The data comprised 2,225 patients treated in Edinburgh (UK), Glasgow (UK), Manchester (UK), or Toronto (Canada), with tumor control assessed after at least 2 years. Heterogeneity in each series was taken into account using the coefficient of variation (CV) of the clonogen radiosensitivity (alpha). Maximum likelihood techniques were used to provide best estimates of the parameters, and also direct estimation of the more stable parameter ratios of interest. RESULTS: The use of different heterogeneity factors for the different series allowed common dose/time parameters to be fitted across all four series in a way not possible using the standard model, enabling the inherent effect of heterogeneity in flattening dose-response curves and in reducing time factors to be separated from the underlying more-representative values. Radiosensitivity CVs were calculated to be 30% (Edinburgh), 36% (Glasgow), 40% (Manchester), and 71% (Toronto). The lag phase was 32 days (95% CL 20-38 days) which was longer than the value of 23 days (11-36 days) deduced using the standard model without the heterogeneity parameter. The time factor was 1.2 (0.8-2.2) Gy/day, again greater than the value of 0.80 (0.54-1.41) Gy/day derived using the standard model. Similar larger time factors and longer lag periods could be reproduced using the standard model either by using a parameterization based on parameter ratios, or by omitting the discordant Toronto data and refitting just the data from the three UK centers. CONCLUSION: It was concluded that the heterogeneity model provides a better representation of the time factor for tumor control when data are analyzed comprising different stages of disease treated at different centers. The model allows different amounts of heterogeneity in different series, which tend to flatten dose-responses curves and reduce time factors, to be taken in to account. Also, direct maximum likelihood estimates can be made of the lag period, the time factor (lambda/alpha), and the fractionation sensitivity (beta/alpha), as well as the clonogen population inactivation dose (lnk)/alpha. Values of these parameter ratios are more robust and stable than the individual parameter values. The results of the present analysis using a total of 2,225 patients from four centers indicate that the average lag period may be somewhat longer and the average time factor somewhat greater (and the 95% confidence limits of the time factor exclude previous estimates), than the values deduced previously using simpler models and more diverse multi-center datasets.

Dose-Response Relationship, Radiation↗

Sexing mammalian sperm for production of offspring: the state-of-the-art.

Predetermination of sex in livestock offspring is in great demand and is of critical importance to providing for the most efficient production of the world's food supply. With the changes that have taken place in animal agriculture over the past generation the application of sex preselection to production systems becomes increasingly necessary. The current technology is based on the well-known difference in X- and Y-sperm in the amount of DNA present. The method has been validated on the basis of live births, laboratory reanalysis of sorted sperm for DNA content and embryo biopsy for sex determination. The technology incorporates modified flow cytometric sorting instrumentation to sort X- and Y-bearing sperm. Resulting populations of X or Y sperm can be used in conjunction with IVF in swine and in cattle for the production of sexed embryos to be transferred to eligible recipients for the duration of gestation. It can also be used for intratubal insemination and for deep-uterine and conventional insemination in cattle. This semipractical sexing method, though currently impractical for some production systems (where large numbers of sperm are required for fertilization) could be used to provide a more flexible progeny-producing option in many livestock operations. Improvements in the production rate of sexed sperm continue as new technology is developed. High-speed sorting is one of the newer technological advances and is being used in our laboratory to increase sorted sperm throughput. With our original technology we sorted 350,000 sperm/h. We now sort 6 million of each sex, under routine conditions. Sorting only the X population results in about 18 million sperm/h. Improvements in the technology will no doubt lead to much greater usage of sexed sperm, depending on the species involved. Insemination of lower sperm numbers in cattle has proven to be an effective means of utilizing the sexing technology. Solving the problems associated with inseminating low sperm numbers in the pig would be advantageous to the utilization of sexed sperm for some type of deep artificial insemination. Such a development would also enhance the economy of using lower sperm numbers with conventional artificial insemination (AI) and aid the swine industry worldwide. The use of sexed sperm for non-ordinary applications such as endangered species, laboratory animals, hobby or pet species is also of interest and will become a part of the move to be more reproductively efficient in the next millennium. Sexed sperm on demand over the next several years will provide livestock producers with many options in seeking to improve efficiency of production and improve quality of products to enhance consumer acceptability.

Animals↗

Clinical features of the early stage of the Rett syndrome.

Our previous reports have pointed out that the Rett syndrome (RS) starts from early infancy with autistic behavior and muscle hypotonia, and we have raised the hypothesis in regard to the pathophysiology that RS can be an early developmental disorder of the monoaminergic and indolamine systems. This paper presents the reanalysis of early motor and behavioral features performed on 16 patients. The most frequent complaint was developmental delay, but 2 cases were presented with autistic behaviors. Development showed delay even from head control. Crawling was particularly difficult. Muscle hypotonia was present in all cases. Early autistic behaviors were seen in high degree and the most frequent was the pervasive lack of social association. Autistic behaviors characterizing older autism were seen in various degrees. These findings reconfirm our previous reports and hypothesis. Furthermore, it can be suggested that the onset may even be in the fetal stage and that lesions of specific neuronal systems occurring in early ontogeny could result in specific abnormality in the higher system which manifest later in development, after these structures reach certain levels of maturation.

Child↗

Stereotaxic needle-core biopsy and fine-needle aspiration biopsy in the diagnosis of nonpalpable breast lesions: controversies and future prospects.

OBJECTIVE: To determine the advantages and limitations of a combined stereotaxic fine-needle aspiration biopsy and needle-core biopsy in the diagnosis of 353 nonpalpable breast lesions with special attention given to the collection of follow-up data. METHODS AND MATERIAL: 353 nonpalpable breast lesions underwent 'one pass' stereotaxic fine-needle aspiration (21 gauge needle) and needle-core biopsy (18 gauge needle) at our institution from January 1990 to October 1993. Stereotaxic biopsies were carried out by means of an 'add-on unit'. Surgical biopsy was usually recommended for highly suspicious radiologic patterns and/or needle biopsy reports classified as atypical or malignant. In all other cases mammographic follow-up was advised at 6 months and then annually for 3 years. The data were collected retrospectively during September 1995 (theoretical average follow-up of greater than 3 years). RESULTS: Following the combined needle biopsy technique procedure, surgery was recommended for 83 lesions. Fifty-four cancers were associated to these suspicious lesions. Because of changing radiological or clinical pattern during follow-up (mean follow-up: 22 months), 11 cancers were detected among the 270 lesions initially considered not to need surgery. Forty-three percent of the 65 malignant lesions were initially read as having less than highly suspicious mammographic features. There was no significant difference between the sensitivity and the specificity of one pass fine-needle aspiration biopsy (57% and 96% respectively) and needle-core biopsy (60% and 97% respectively), but noncontributive samples were not included in the false negative diagnoses and atypical samples were included in the true positive diagnoses. Of the 11 missed cancers, nine were manifested initially by clusters of calcifications. Our diagnostic approach was significantly less sensitive (P = 0.006) and less specific (P = 0.032) in cases of clusters of calcifications (31% false negative diagnoses) than in cases of soft-tissue masses (5.5% false negative diagnoses). In this study, an average delay in diagnoses of 22 months was responsible for a significantly increased percentage of axillary node positive invasive cancer (P < 0.001) and six of the 11 missed cancers were palpable at the time of the delayed diagnosis. For the nine cancers initially manifested by calcifications, the 22 months delay in diagnosis was responsible for a nonsignificant increase of microinvasive type at the expense of carcinoma in situ. CONCLUSION: Our enthusiasm with the sensitivity of this double stereotaxic needle sampling has been tempered by the results of this reanalysis in the light of a mean theoretical follow-up of three years. Our diagnostic approach was adequate in the presence of soft-tissue masses but not valid in the presence of clustered calcifications. When dealing with calcifications, multiple samplings must be done in order to improve the sensitivity of the diagnosis. Furthermore, this study does not favour the theory that the majority of mammographically detected cancers are indolent and highlights the poor sensitivity of the mammographic follow-up of nonpalpable lesions.

Biopsy, Needle↗

Carotid artery stenosis: preoperative noninvasive evaluation in a community hospital.

PURPOSE: The purpose of this study was to determine whether noninvasive evaluation with duplex ultrasonography and magnetic resonance angiography of patients with carotid artery stenosis can replace contrast angiography at our institution. METHODS: This study consisted of a retrospective chart review of 40 patients (74 carotid arteries) in combination with a blinded reanalysis of original data. Contrast angiography was compared with duplex ultrasonography and magnetic resonance angiography. The overall diagnostic accuracy of duplex ultrasonography and magnetic resonance angiography was determined individually and concordantly in patients being evaluated for carotid artery stenosis. RESULTS: The overall sensitivity of duplex ultrasonography was 88.5%, and the specificity was 91.7% (Spearman correlation coefficient = 0.8456; p < 0.001). For magnetic resonance angiography the sensitivity was 92.3%, and the specificity was 97.9% (Spearman correlation coefficient = 0.9086; p < 0.001). In the presence of concordance, the noninvasive studies exhibited a sensitivity of 100%, (correlation coefficient = 0.9661; kappa value = 0.9655). No occlusions or severe lesions were missed by both studies. In only one vessel (1.52%) was a false-positive concordance noted. CONCLUSIONS: Carotid endarterectomy may be undertaken with a high degree of confidence that the operation will be appropriate if the noninvasive evaluations are concordant. In the absence of concordance of the noninvasive studies, contrast angiography should be considered.

Aged↗

Female sterilization. Evidence.

The literature review herein reveals substantial information regarding the safety, efficacy, short-term complications, long-term complications, and noncontraceptive benefits of sterilization. This information should be helpful for providers and potential sterilization candidates. The review also reveals areas where the data are unclear. Points to keep in mind during counseling include the following: The vast majority of women are satisfied with the decision to undergo sterilization. The fact that regret occurs underscores the importance of counseling and adequate individual deliberation before the procedure. In addition to the difficulty and expense associated with sterilization reversal, the woman should thoroughly understand the permanence of the procedure. Although failure is a rare event, it can occur many years after the procedure. Although evidence suggests that hysterectomy rates are higher in sterilized women aged less than 30 to 35 years, it is unlikely that there is a plausible biologic effect of sterilization on hysterectomy risk. An association between tubal sterilization and menstrual cycle changes does not seem valid for changes noted up to 2 years after the procedure. Data are unclear and inconsistent among studies observing women more than 2 years after the procedure. Evidence consistently shows that sterilization is associated with a reduced incidence of ovarian cancer and pelvic inflammatory diseases. Most studies show no effect or improvement of sexual satisfaction after sterilization. Complications during and postprocedure are rare. Sterilization provides no protection against the acquisition of sexually transmitted disease. Patients and their physicians should recognize that sterilized women may need more targeted preventive efforts for health screening and to reduce high-risk behavior than women who use other contraceptive methods. The surgeon's experience and the woman's preferences should govern the ultimate decision regarding the approach and occlusion method. Level II-2 evidence indicates comparable safety between interval laparoscopy and minilaparotomy. Data consistently show that in experienced trained hands, tubal sterilization is safe and highly effective regardless of the approach or occlusive method. Attention to the subtleties of technique seems to be most important in ensuring procedure safety and efficacy. Reanalysis of the CREST data shows that the cumulative failure rate of bipolar coagulation is comparable with the failure rate of unipolar coagulation if a substantial length of tube is adequately coagulated. The data discussed herein can be used to guide management decisions that may increase accessibility and reduce cost of the procedure. Low-resource settings and office settings have maintained an excellent safety record for this procedure through performance of sterilization under local anesthesia. The use of local anesthesia enables a change in procedure location from an inpatient operating room to a free-standing surgical clinic or adequately equipped office. Local anesthesia, with or without preoperative medication, is an excellent option associated with a lower complication risk, reduced cost, and shorter, easier recovery. The surgeon should have specific training in the effective use of local anesthetics, preoperative medications, and management of rare complications in low-resource settings. Little additional research is needed regarding the safety and efficacy of standard sterilization approaches and occlusion methods. There is a need for continued development of nonsurgical methods of sterilization, microlaparoscopic approaches performed in the office setting, and the feasibility and acceptance of service provision by nonspecialist health care providers. The evidence indicates that female sterilization can be performed safely in a variety of resource settings ranging from rural sterilization camps in developing countries to high-tech, resource-rich operating rooms in developed c

Abortion, Induced↗

Body-rocking in college students and persons with mental retardation: characteristics, stability, and collateral behaviors.

Body-rocking was analyzed in four studies. The first showed that rocking chairs are not necessarily preferred by people with mental retardation, and that a rocking chair produces a higher amplitude of body-rocking. A second study demonstrated the stability of various measures of body-rocking over a 21-month period. Stable idiosyncratic behaviors accompanying body-rocking also were described. The third study showed that, when compared with college students who engage in habitual body-rocking, persons with mental retardation engage in more body-rocking than college students on various dimensions, and that they also show different collateral behaviors. Finally, in the fourth study, a reanalysis of the data from Study I showed that collateral behaviors do not necessarily occur as part of a body-rocking complex.

Adult↗

Evaluation of diagnostic imaging tests: diagnostic probability estimation.

In the evaluation of a diagnostic imaging test for the diagnosis of a particular illness in a particular category of patients, the test should be construed as leading to a test result in the sense of a set of descriptive readings from the image(s), not interpretation of these; and in the evaluation of the test, therefore, the first challenge is the translation of each test result (set of readings) into the corresponding probability that the illness is present. This interpretive translation should not be subjective, nor should it be based on an objective algorithm founded on clinical judgments. Instead, a suitable diagnostic probability function (of the elements in the test result) should be derived empirically by logistic regression analysis of suitable data. We illustrate this alternative outlook by reanalysis of the data from the Prospective Investigation of Pulmonary Embolism Diagnosis.

Adult↗

Problems with using capture-recapture in epidemiology: an example of a measles epidemic.

Capture-recapture is becoming widely used in epidemiology to estimate disease prevalence or sizes of population at risk. When such estimates are obtained from uncontrolled observation of existing lists, a huge act of faith is required, usually without any scientific justification. Fitting of loglinear models appears to offer some hope but contains major problems of analysis and interpretation. These are illustrated by reanalysis of data on a measles epidemic-see McGilchrist et al. 1996 [J Clin Epidemiol 49, pp. 293-296]--for which the wrong model was selected. It is argued that the measles lists contained so few overlaps that no reliable information is provided by that study about the size of the epidemic.

Australia↗

Negative association of schizophrenia with HLA DQB1*0602: evidence from a second African-American cohort.

The authors attempted a replication of an earlier study of African-Americans, in which they detected a negative association of schizophrenia with HLA DQB1*0602. Patients with schizophrenia (n = 75, DSM-III-R criteria) and screened adult controls of African-American ethnicity (n = 66) were genotyped with respect to HLA DQB1*0602 using a combination of two polymerase chain reaction (PCR) based assays: amplification with sequence specific primers and a dot blot assay. A significant negative association with HLA DQB1 was not noted overall, but was present among women (female patients vs. female controls: odds ratio, OR = 0.42, 95% confidence intervals, CI = 0.32, 0.55). Reanalysis of the earlier study also revealed a gender related association. When the present and earlier samples from both genders were combined, the association persisted (OR 0.48; 95% CI: 0.12, 0.52). The present findings support and association between schizophrenia and the HLA DQB1 gene locus among African-Americans.

Adult↗

Syntactic parsing preferences and their on-line revisions: a spatio-temporal analysis of event-related brain potentials.

The present study investigates the processes involved in the recovery from temporarily ambiguous garden-path sentences. Event-related brain potentials (ERP) were recorded while subjects read German subject-object ambiguous relative and complement clauses. As both clause types are initially analyzed as subject-first structures, object-first structures require a revision which is more difficult for complement than for relative clauses. The hypothesis is tested that the revision process consists of two sub-processes, namely diagnosis and actual reanalysis. Applying a spatio-temporal principal component analysis to the ERP data, distinct positive sub-components presumably reflecting different sub-processes could be identified in the time range of the P300 and P600. It will be argued that the P600 is not a monolithic component, and that different sub-processes may be involved at varying time points depending on the type of garden-path sentence.

Adult↗

Is human sentence parsing serial or parallel? Evidence from event-related brain potentials.

In this ERP study we investigate the processes that occur in syntactically ambiguous German sentences at the point of disambiguation. Whereas most psycholinguistic theories agree on the view that processing difficulties arise when parsing preferences are disconfirmed (so-called garden-path effects), important differences exist with respect to theoretical assumptions about the parser's recovery from a misparse. A key distinction can be made between parsers that compute all alternative syntactic structures in parallel (parallel parsers) and parsers that compute only a single preferred analysis (serial parsers). To distinguish empirically between parallel and serial parsing models, we compare ERP responses to garden-path sentences with ERP responses to truly ungrammatical sentences. Garden-path sentences contain a temporary and ultimately curable ungrammaticality, whereas truly ungrammatical sentences remain so permanently--a difference which gives rise to different predictions in the two classes of parsing architectures. At the disambiguating word, ERPs in both sentence types show negative shifts of similar onset latency, amplitude, and scalp distribution in an initial time window between 300 and 500 ms. In a following time window (500-700 ms), the negative shift to garden-path sentences disappears at right central parietal sites, while it continues in permanently ungrammatical sentences. These data are taken as evidence for a strictly serial parser. The absence of a difference in the early time window indicates that temporary and permanent ungrammaticalities trigger the same kind of parsing responses. Later differences can be related to successful reanalysis in garden-path but not in ungrammatical sentences.

Adult↗

An investigation of the intra-generic structure of Rothia by pyrolysis mass spectrometry.

Previous studies of the genus Rothia have indicated that members of the only species, Rothia dentocariosa, are heterogeneous and may form more than one species. To study the intrageneric taxonomic structure of the Rothia taxon eighteen strains identified as R. dentocariosa, including reference organisms from culture collections (3 strains), isolates from healthy subjects (5 strains) and from clinical sources (10 strains) were examined using pyrolysis mass spectrometry. The ordination plots of the pyrolysis data indicated that all the strains clustered in a closely related group, with the exception of three strains which out-grouped. Phenotypic testing and fatty acid data indicated that the latter three strains are probably misclassified in the genus Rothia. Reanalysis of the PyMS data including only the fifteen authentic Rothia strains indicated that ten of these organisms formed a group which included the type strain, R. dentocariosa NCTC 10917. Four out of the remaining five organisms formed a diffuse group; the remaining strain was recovered as a single member cluster. These data indicate that R. dentocariosa is heterogeneous though at present there are no suitable criteria for assigning members of this taxon to more than one species.

Actinomycetales↗

Iterative data analysis is the key for exhaustive analysis of peptide mass fingerprints from proteins separated by two-dimensional electrophoresis.

Peptide mass fingerprinting (PMF) is a powerful tool for identification of proteins separated by two-dimensional electrophoresis (2-DE). With the increase in sensitivity of peptide mass determination it becomes obvious that even spots looking well separated on a 2-DE gel may consist of several proteins. As a result the number of mass peaks in PMFs increased dramatically leaving many unassigned after a first database search. A number of these are caused by experiment-specific contaminants or by neighbor spots, as well as by additional proteins or post-translational modifications. To understand the complete protein composition of a spot we suggest an iterative procedure based on large numbers of PMFs, exemplified by PMFs of 480 Helicobacter pylori protein spots. Three key iterations were applied: (1) Elimination of contaminant mass peaks determined by MS-Screener (a software developed for this purpose) followed by reanalysis; (2) neighbor spot mass peak determination by cluster analysis, elimination from the peak list and repeated search; (3) re-evaluation of contaminant peaks. The quality of the identification was improved and spots previously unidentified were assigned to proteins. Eight additional spots were identified with this procedure, increasing the total number of identified spots to 455.

Cluster Analysis↗

The influence of cigarette smoking on the association between body weight and mortality. The Framingham Heart Study revisited.

PURPOSE: To calculate for two measures of obesity, the Metropolitan Relative Weight (MRW) and body mass index (BMI), the value at which minimum mortality occurs. This was done to retest the hypothesis, in the Framingham Heart Study data, that the association between obesity and mortality can be obscured by an interaction between the measure of obesity and smoking. In the original analysis of the Framingham data it was suggested that there was a U- or J-shaped relationship between MRW and death in smokers but a linear relationship in nonsmokers. The design and setting were those of the NHLBI Framingham Heart Study. METHODS: The 5209 members of the Framingham Heart Study underwent a baseline examination in 1948-1952 (Exam 1) and they were reexamined at approximately two-year intervals over a 30-year period. The study included both men (n = 2336) and women (n = 2873) in the age range of 28 to 62 years. After excluding persons with missing baseline data, the analytic sample size was 5163. Additional analyses were conducted by deleting persons with cardiovascular disease (CVD) at baseline (n = 135), the sample used by the original paper by Garrison and colleagues, and persons who died within the first four years of follow-up (n = 62). The main outcome measures consisted of thirty-year survival through Exam 16, approximately in 1980, as influenced by MRW or BMI, age, and smoking status at baseline (Exam 1). RESULTS: We were able to show that the sample sizes of male nonsmokers were too small to test the hypothesis within age groups < 40 and 40-49 years. In men ages 50-62 there was a significant age-adjusted quadratic relationship between BMI or MRW, and risk of death. The estimated BMI at the minimum risk of death for smokers (24.5) and nonsmokers (23.8) were not statistically different. Identical results were found for MRW (minimum: smokers = 112.5, nonsmokers = 111.4). In men and women ages 28-62 there appeared to be a u- or j-shaped relationship between the 30-year crude mortality rate and MRW. After excluding persons with missing data, CVD at baseline, and persons who died within the first four years of follow-up, the age adjusted estimated BMI value at the minimum risk of death was nearly identical for men and women and for smokers and nonsmokers (Men: smokers = 22.8, nonsmokers = 22.8; Women: smokers = 22.9, nonsmokers = 23.3). Additionally, the estimates of the minimum were always below the mean. Identical results were found without deleting persons with CVD at baseline and deaths in the first four years of follow-up. Identical results were found for MRW. CONCLUSIONS: Reanalysis of the Framingham Heart Study data does not support the hypothesis that there is an interaction between smoking and measures of obesity. Moreover, the estimated BMI or MRW at the minimum risk of death was similar for men and women smokers and nonsmokers alike even after deleting prevalent cases of CVD and deaths within the first four years of follow-up.

Adult↗

Incidental appendectomy in the era of managed care and laparoscopy.

BACKGROUND: In a study carried out before laparoscopy or managed care, there was no cost or patient benefit for routine incidental appendectomy. With the onset oflaparoscopy, a change in indications for surgery, and increased prevalence of capitated contracts, a reanalysis of the cost-effectiveness of incidental appendectomy is warranted. STUDY DESIGN: Financial data from 251 patients undergoing appendectomy for acute appendicitis without complication at a single institution were identified. Age-specific epidemiology data from the Centers for Disease Control, Atlanta, were applied to assess risk and cost of future appendectomy. The net cost or savings for incidental appendectomies necessary to prevent one case of acute appendectomy was determined and stratified by gender and age to the population as a whole. Further adjustment was made for the variable level of surgeon reimbursement for incidental appendectomy. RESULTS: At 10% surgeon reimbursement, open incidental appendectomy was cost-effective in those less than 25 years of age (< 35 years of age in a capitated system). Applied to the general population, open incidental appendectomy in those less than 25 years represented savings of up to $1,100 per 10,000 population per year. A surgeon fee of greater than 50%, or the laparoscopic approach using staplers, accrued no savings in any age groups. CONCLUSIONS: Open incidental appendectomy at low physician reimbursement is a cost-effective procedure for patients of less than 35 years of age. A decrease in equipment cost for laparoscopic approach will extend these indications.

Acute Disease↗

Hepatic resection for metastatic colorectal adenocarcinoma: a proposal of a prognostic scoring system.

BACKGROUND: Hepatic resection for metastatic colorectal cancer provides excellent longterm results in a substantial proportion of patients. Although various prognostic risk factors have been identified, there has been no dependable staging or prognostic scoring system for metastatic hepatic tumors. STUDY DESIGN: Various clinical and pathologic risk factors were examined in 305 consecutive patients who underwent primary hepatic resections for metastatic colorectal cancer. Survival rates were estimated by the Cox proportional hazards model using the equation: S(t) = [So(t)]exp(R-Ro), where So(t) is the survival rate of patients with none of the identified risk factors and Ro = 0. RESULTS: Preliminary multivariate analysis revealed that independently significant negative prognosticators were: (1) positive surgical margins, (2) extrahepatic tumor involvement including the lymph node(s), (3) tumor number of three or more, (4) bilobar tumors, and (5) time from treatment of the primary tumor to hepatic recurrence of 30 months or less. Because the survival rates of the 62 patients with positive margins or extrahepatic tumor were uniformly very poor, multivariate analysis was repeated in the remaining 243 patients who did not have these lethal risk factors. The reanalysis revealed that independently significant poor prognosticators were: (1) tumor number of three or more, (2) tumor size greater than 8 cm, (3) time to hepatic recurrence of 30 months or less, and (4) bilobar tumors. Risk scores (R) for tumor recurrence of the culled cohort (n = 243) were calculated by summation of coefficients from the multivariate analysis and were divided into five groups: grade 1, no risk factors (R = 0); grade 2, one risk factor (R = 0.3 to 0.7); grade 3, two risk factors (R = 0.7 to 1.1); grade 4, three risk factors (R= 1.2 to 1.6); and grade 5, four risk factors (R > 1.6). Grade 6 consisted of the 62 culled patients with positive margins or extrahepatic tumor. Kaplan-Meier and Cox proportional hazards estimated 5-year survival rates of grade 1 to 6 patients were 48.3% and 48.3%, 36.6% and 33.7%, 19.9% and 17.9%, 11.9% and 6.4%, 0% and 1.1%, and 0% and 0%, respectively (p < 0.0001). CONCLUSIONS: The proposed risk-score grading predicted the survival differences extremely well. Estimated survival as determined by the Cox proportional hazards model was similar to that determined by the Kaplan-Meier method. Verification and further improvements of the proposed system are awaited by other centers or international collaborative studies.

Adenocarcinoma↗