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PubMed1988

The effect of transurethral resection on prognosis in carcinoma of the prostate: real or imaginary?

From January 1970 to June 1983, a total of 702 patients received radical external beam radiation therapy for carcinoma of the prostate. The estimated 5- to 10-year disease-free survival are 67% and 52%. A comparison was made between those patients whose diagnosis was established by needle biopsy as compared with those who had a positive transurethral resection of the prostate (TURP). Within Stages B & C combined, the 5-year disease-free survival was 65% for needle biopsy as compared with 59% for TURP. The corresponding figures at 10 years are 50% and 43%. This difference is significant with a p-value of less than 0.01. In addition to histological grade, identifiable prognostic factors in the literature are clinical stage, serum acid phosphatase, and extent of radiation (local only or prophylactic pelvic nodal radiation). Assessment of histological grade using the Gleason method has been carried out in all except 7 cases. The amount of tissue from a needle biopsy constitutes less than 3% of the material obtained from a TURP. As a result, there is a potential sampling error. The Gleason grading can be used in at least three ways: (a) the conventional Gleason score, (b) the most malignant grade identified, or, (c) the primary (most frequent) grade identified. Analyzing use of these three methods of histological stratification yields conflicting results. The difference between the needle and TURP groups is present in late stage disease when the primary grade is used for stratification but absent when the worst grade is used. The significance of these results remains more or less constant irrespective of end point (uncorrected, disease specific or disease-free survival). However, when stratified by Gleason score, it is significant for disease specific survival, approaches significance for uncorrected survival but not for disease free survival. Since the significance can be altered by changing one stratification factor, there must be some doubt about the validity of other studies which either confirm or refute the hypothesis that TURP has an adverse influence on the disease process.

Aged↗
PubMed1992

The significance of post-irradiation prostate biopsy with long-term follow-up.

Ninety-four patients, Stage A2-C, definitively irradiated for adenocarcinoma of the prostate from 1975 to 1981 underwent digitally directed transperineal needle biopsy of a clinically negative prostate gland at least 18 months post-therapy. Ten of 55 patients (18%) treated with Iodine-125 implantation and 7 of 39 patients (18%) externally irradiated were found to have positive biopsy specimens. Overall, clinical local failure occurred in 53% of patients with positive biopsy results but in only 18% with negative specimens, p = .006. The false negative biopsy rate in patients treated with I-125 was nearly three times that for external beam, 24% versus 9%, perhaps because of the greater possibility of inhomogeneous dose distribution with I-125, allowing for a higher degree of sampling error. Actuarial local failure at 5 years was 44% versus 8% with positive and negative biopsies, respectively, and 75% versus 24% at 10 years (p = .0001). The distant metastatic rate was twice as high in biopsy-positive as compared to biopsy-negative patients, 71% versus 35%, p = .015. Actuarially, only 19% of patients with a positive biopsy are NED at 10 years as compared to 62% of those with a negative biopsy (p = .0001). PSA values are supportive in those patients thought to be disease-free. The incidence of positive biopsy and associated local recurrence are in keeping with clinical treatment failure rates as reported in multiple studies to date.

Adenocarcinoma↗
PubMed1991

Sensitive method for the determination of vincristine in human serum by high-performance liquid chromatography after on-line column-extraction.

A column-switching high-performance liquid chromatographic method was developed for the determination of vincristine in serum. Sample preparation was carried out by means of on-line column-extraction, using a C18 reversed-phase preconcentration column. This technique is simple (minimizing manual sampling errors), rapid (reduction of time and costs) and can be easily automated. Both ultraviolet and electrochemical detection are possible, but the latter shows a cleaner chromatogram and is, by the use of a new electrochemical detector, far more sensitive (detection limit 0.3 microgram/l at a signal-to-noise ratio of 3). A matrix study was carried out (using human serum and urine and two kinds of calf's serum). Although it appeared that the system was matrix-dependent, no difference in matrix effects could be found in the serum or plasma of different patients. Controls for human serum analysis should be prepared in human serum. With the method described, pharmacokinetic studies of vincristine in children can be performed.

Chromatography, High Pressure Liquid↗
PubMed1994

High-performance liquid chromatographic method for the simultaneous determination of low-molecular-mass oligomers of polyethylene glycol in aqueous skin extracts.

The isocratic, reversed-phase, high-performance liquid chromatographic (HPLC) method presented provides a simple and rapid analytical technique for the simultaneous determination of low-molecular-mass oligomers of polyethylene glycol (PEG) in aqueous polymer samples containing polar contaminants of biologic origin. In the present case, individual molecular mass species were quantitated in aqueous skin extracts arising from the investigation of PEG transport through mammalian skin. PEGs were isolated and purified by solid-phase extraction using large-pore kieselguhr (Extrelut QE) cartridges, which selectively retained polar contaminants from excised skin specimens. Sample recoveries were found to be dependent upon molecular mass, ranging from 18.28% to 86.10%, but were highly reproducible. The mean inter-sample error (n > or = 5) for the extraction of twenty-six molecular mass species of PEG was less than 3%. Satisfactory resolution of primary molecular mass components was accomplished using a base-deactivated, C8 column (Supelcosil LC-8-DB) and a mobile phase consisting of methanol and water. Corresponding run times for the complete separation of individual oligomers ranged from 8 to 30 min, while the limit of detection for a particular molecular mass species was approximately 5 micrograms/ml. The method was further employed to determine the weight-average (Mw) and number-average (Mn) molecular mass distributions and polydispersity for three commercial PEG blends, as well as to characterize the methylene chloride/water distribution coefficients for twenty-two molecular mass species ranging from 282 to 1206 Da.

Animals↗
PubMed1994

DNA profile match probability calculation: how to allow for population stratification, relatedness, database selection and single bands.

In DNA profile analysis, uncertainty arises due to a number of factors such as sampling error, single bands and correlations within and between loci. One of the most important of these factors is kinship: criminal and innocent suspect may share one or more bands through identity by descent from a common ancestor. Ignoring this uncertainty is consistently unfair to innocent suspects. The effect is usually small, but may be important in some cases. The report of the US National Research Committee proposed a complicated, ad-hoc and overly-conservative method of dealing with some of these problems. We propose an alternative approach which addresses directly the effect of kinship. Whilst remaining conservative, it is simple, logically coherent and makes efficient use of the data.

Alleles↗
PubMed1986

Comparative evaluation of PathoDx Strep A test and culture for the detection of group A streptococci in pharyngeal specimens.

The PathoDx Strep A kit, a 10-min acid extraction and latex agglutination test, was compared with routine culture for the direct detection of group A beta-hemolytic streptococci (BHS) in 414 pharyngeal specimens collected from children with pharyngitis. The results showed that the latex test compared favorably with culture for detecting group A BHS in pharyngeal specimens (sensitivity 96.7%, specificity 97.9%, and positive and negative predictive values of 97.2% and 97.4%, respectively). The comparable number of false-positive (five) and false-negative (six) latex tests along with review of patient histories suggest that these discrepant results were attributable to sampling error during specimen procurement rather than deficiencies in the latex kit. In addition, clear-cut, agglutination reactions were obtained in over 96% of positive latex tests regardless of the amount of group A BHS that was recovered by culture. The PathoDx Strep A test is a rapid, reliable noncultural alternative for the detection of group A BHS in pharyngeal specimens.

Antigens, Bacterial↗
PubMed1995

CT and MRI of diffuse liver disease.

CT and MRI contribute important information to the clinical evaluation of diffuse liver disease. In some cases, these modalities can establish a diagnosis that was not ascertained histologically, which is often the case when sampling errors prevent a definitive tissue diagnosis. Characteristic alterations of liver attenuation on CT, signal changes on MRI, and morphological changes appreciated with both modalities can be used to diagnose fatty infiltration, some parenchymal deposition diseases, and cirrhosis. Furthermore, hepatocellular disease can be confirmed in the setting of indeterminate clinical and laboratory findings. Significant overlap in the imaging findings of this wide range of disorders continues to limit specificity; however, at a minimum, these techniques provide a rapid means to a noninvasive evaluation that often guides clinical decisions. Faster scanning techniques available with CT and MRI may provide additional information by assessing contrast dynamics. This review of CT and MRI in diffuse liver disease considers the diagnostic utility and clinical implications of these modalities. Pathological findings relevant to imaging considerations are discussed.

Fatty Liver↗
PubMed2005

New fluorescence markers to distinguish co-infecting Trypanosoma brucei strains in experimental multiple infections.

Multiple-genotype infections are increasingly recognized as important factors in disease evolution, parasite transmission dynamics, and the evolution of drug resistance. However, the distinction of co-infecting parasite genotypes and the tracking of their dynamics have been difficult with traditional methods based on various genotyping techniques, leaving most questions unaddressed. Here we report new fluorescence markers of various colours that are inserted into the genome of Trypanosoma brucei to phenotypically label live parasites of all life cycle stages. If different parasite strains are labelled with different colours they can be easily distinguished from each other in experimental studies. A total of 10 T. brucei strains were successfully transfected with different fluorescence markers and were monitored in culture, tsetse flies and mice, to demonstrate stability of marker expression. The use of fluorescence activated cell sorting (FACS) allowed rapid and accurate identification of parasite strains labelled with different markers. Cell counts by FACS were virtually identical to counts by traditional microscopy (n=75, Spearman's rho: 0.91, p<0.0001) but were considerably faster and had a significantly lower sampling error (66% lower, d.f.=73, t=-17.1, p<0.0001). Co-infecting strains transfected with fluorescence genes of different colour were easily distinguished by eye and their relative and absolute densities were reliably counted by FACS in experimental multiple infections in mice. Since the FACS can simultaneously determine the population sizes of differently labelled T. brucei strains or subspecies it allows detailed and efficient tracking of multiple-genotype infections within a single host or vector individual, enabling more powerful studies on parasite dynamics. In addition, it also provides a simple way to separate genotypes after experimental mixed infections, to measure responses of the single strains to an applied treatment, thus eliminating the need for laborious cloning steps. The markers presented broaden the spectrum of tools available for experimental studies on multiple-genotype infections. They are fundamentally different from isoenzyme analysis and other genotyping approaches in that they allow the distinction of parasite genotypes based on an easily recognizable phenotypic trait. They will be of specific interest to researches addressing ecological, evolutionary and epidemiological questions using trypanosomes as an experimental system.

Animals↗
PubMed2004

Local recurrence in lumpectomy patients after imprint cytology margin evaluation.

BACKGROUND: This is a follow-up study to our previously reported data on local recurrence rates in patients whose lumpectomy margins were evaluated by intraoperative imprint cytology (IIC(M)). The purpose of this study was to compare local recurrence rates for patients whose lumpectomy margins were evaluated with IIC(M) with local recurrence rates of those not evaluated by IIC(M). METHODS: A total of 1713 patients underwent lumpectomy treatment for breast cancer from 1988 to 2001 were prospectively entered into a computerized database and subsequently included in this study. Of the patients, 520 (group 1) had their surgery performed at an outside institution where conventional margin analysis was performed. Another 1193 (group 2) had their surgery performed at our institution where margins were evaluated by IIC(M). For each histologic type and for the overall sample, probabilities of recurrence with time were estimated using the method of Kaplan and Meier. RESULTS: IIC(M) overcomes sampling error inherent in the frozen section analysis and results in a diminished incidence of overall 5-year local recurrence from 8.8% to 2.8% (P <0.0001). The recurrence rates for each respective histologic subtype are reported for both absolute recurrences and probability of recurrence with time. CONCLUSIONS: IIC(M) provides an accurate evaluation of lumpectomy margins for patients undergoing breast-conservation treatment. IIC(M) was associated with an overall lower local recurrence rate. This series defined the utility of intraoperative imprint cytology for evaluation of margins in patients undergoing breast-conservation treatment.

Breast Neoplasms↗
PubMed2004

Frozen section diagnoses of small pulmonary nodules: accuracy and clinical implications.

BACKGROUND: Pulmonary nodules are frequently first diagnosed by frozen section, immediately followed by lobectomy or other procedures. The frozen section diagnosis of pulmonary nodules can be difficult, as inflammatory and fibrotic lesions can be confused for malignancy, creating intraoperative dilemmas for pathologists and thoracic surgeons. METHODS: We reviewed our experience at Cedars-Sinai Medical Center with the frozen section diagnoses of 183 consecutive pulmonary nodules smaller than 1.5 cm in diameter and calculated the sensitivity, specificity, and predictive values of this diagnostic procedure. RESULTS: One hundred and seventy four nodules were correctly classified by frozen section as neoplastic or nonneoplastic, six lesions were diagnosed equivocally, and two neoplasms were missed owing to sampling errors. The equivocal frozen section diagnoses included two bronchioloalveolar carcinomas (BAC) interpreted as "atypical hyperplasia, favor BAC," two BAC diagnosed as "alveolar hyperplasia," and two carcinoid tumors labeled as "atypical carcinoma" and "spindle cell lesion, carcinoid versus sclerosing hemangioma," respectively. The sensitivities for a diagnosis of neoplasia were 86.9% and 94.1% for nodules smaller than 1.1 cm in diameter and measuring 1.1 to 1.5 cm, respectively. The diagnostic accuracy of frozen sections was significantly better in nodules larger than 1.0 cm in diameter (p = 0.05). There were no false-positive diagnoses of malignancy, resulting in 100% specificity. CONCLUSIONS: Intraoperative consultation with frozen section is a sensitive and specific procedure for the diagnosis of malignancy from small pulmonary nodules. The distinction between BAC and atypical adenomatous hyperplasia, and of small peripheral carcinoid tumors from other lesions, can be difficult by frozen section. Thoracic surgeons need to become aware of these problems and develop appropriate therapeutic strategies.

Adenocarcinoma, Bronchiolo-Alveolar↗
PubMed2006

Regression of myelofibrosis and osteosclerosis following hematopoietic cell transplantation assessed by magnetic resonance imaging and histologic grading.

Myelofibrosis is a reactive, often inhomogeneous process in the marrow cavity, and sampling errors on biopsies obtained to diagnose and monitor the course of myelofibrosis have been a constant problem in hematopathology. We investigated the potential utility of magnetic resonance imaging (MRI) of the lumbar spine, pelvis, and femora as a diagnostic and monitoring technique for assessment of myelofibrosis. Findings on serial marrow biopsies were correlated with T1-weighted spin-echo and short inversion time inversion recovery (STIR) images in patients with chronic idiopathic myelofibrosis or myelofibrosis developing from polycythemia vera or essential thrombocythemia who underwent hematopoietic cell transplantation (HCT). Thirty-five patients were studied before HCT; 11 were followed for 3 months and 10 patients for >/=1 year after HCT with sequential marrow biopsies and MRI studies. MRI allowed direct visualization of the biopsy sites and correlation of histologic and MRI findings. MRI also provided assessment of the extent and degree of myelofibrosis in a large volume of the skeletal marrow. There was good correlation between biopsy results and MRI findings at specific biopsy sites and between successful HCT and resolution of fibrosis and osteosclerosis as determined by MRI. We conclude that in patients with myelofibrosis, MRI of the skeleton provides a comprehensive assessment of the pattern and extent of fibrosis and allows for correlation with biopsy findings. In patients undergoing HCT, MRI accurately reflects response or progression of marrow disease.

Adult↗
PubMed2005

Endoscopic detection of early upper GI cancers.

The detection of early-stage neoplastic lesions in the upper GI tract is associated with improved survival and the potential for complete endoscopic resection that is minimally invasive and less morbid than surgery. Despite technological advances in standard white-light endoscopy, the ability of the endoscopist to reliably detect dysplastic and early cancerous changes in the upper GI tract remains limited. In conditions such as Barrett's oesophagus, practice guidelines recommend periodic endoscopic surveillance with multiple biopsies, a methodology that is hindered by random sampling error, inconsistent histopathological interpretation, and delay in diagnosis. Early detection may be enhanced by several promising diagnostic modalities such as chromoendoscopy, magnification endoscopy, and optical spectroscopic/imaging techniques, as these modalities offer the potential to identify in real-time lesions that are inconspicuous under conventional endoscopy. The combination of novel diagnostic techniques and local endoscopic therapies will provide the endoscopist with much needed tools that can considerably enhance the detection and management of early stage lesions in the upper GI tract.

Barrett Esophagus↗
PubMed2006

Spectroscopy and fluorescence in esophageal diseases.

Malignant tumors of the esophagus continue to be a major health issue associated with high mortality primarily because most present with symptoms of dysphagia or anaemia. The disease at that stage is advanced and not likely curable. The big issue for squamous dysplasia and that associated with BE is that only a small proportion are discovered in surveillance programs when they are asymptomatic, either because the patient lives in a high-incidence geographical area, has a family history, previously diagnosed head and neck cancer or chronic reflux, as in Barrett's. Current endoscopic methods are hampered by the endoscopist's inability to recognize subtle topographic clues of dysplasia, sampling errors related to biopsy protocols, and confounding inflammation-induced artifacts both for the endoscopist and pathologist. What is desperately needed would be a biomarker (e.g. serological, fecal, urinary) that selects patients for endoscopy. However, such a test is not yet on the horizon. This article examines the current status in practice and research of novel optically based 'bioendoscopic' devices (i.e. fluorescence spectroscopy and imaging, confocal fluorescence microendoscopy (CFM), light scattering spectroscopy (LSS), Raman spectroscopy (RS), and immunophotodiagnostic endoscopy) which may enhance the diagnosis of dysplasia in all patients undergoing conventional white light endoscopy. Perhaps these new technologies will lead to more cost-effective diagnosis, mapping (e.g. surface), and staging (e.g. depth) of dysplasia, thereby allowing timely cure by endoscopic means (e.g. EMR and/or PDT), biological interventions (e.g. Cox-2 inhibitors) rather than esophajectomy.

Endoscopy, Gastrointestinal↗
PubMed2006

Ozone exposure, defoliation of beech (Fagus sylvatica L.) and visible foliar symptoms on native plants in selected plots of South-Western Europe.

The relationships between crown defoliation of beech, visible foliar symptoms on native vegetation and ozone exposure were investigated on permanent monitoring sites in South-Western Europe in the years 2000-2002. Relationships between defoliation of beech and O3 (seasonal mean, 2-week maximum, AOT40) were investigated by means of multiple regression models (11 plots, 1-3 years of data each) and a model based on temporal autocorrelation of defoliation data (14 plots, 1-3 years of data each). Different multiple regression techniques were used. The four models generated (R2=0.71-0.85, explained variance in cross-validation 61-78%) identified several significant predictors of defoliation, with AOT40 (p=0.008) and foliar content of phosphorous (p=0.0002-0.0004) being common to all models. The autocorrelation model (R2=0.55; p<0.0001) was used to calculate expected defoliation on the basis of the previous year's defoliation, and model predictions were used as an estimate of expected defoliation under constant site and environmental condition. Residuals (predicted-measured) plotted against current AOT40 shows that a possible effect of ozone occurs only at very high AOT40 (>35,000 ppbh). O3-like visible foliar symptoms were recorded on 65 species at 47% of the common monitoring sites in 2001 and 38% in 2002. No relationship was found between O3 exposure, frequency of symptomatic sites and frequency of species with symptoms (R2=0.11; p>0.05). A number of questions related to the ecological and methodological basis of the survey were identified. Inherent sampling and non-sampling errors and multicollinearity of the data suggest great caution when examining results obtained from mensurational, correlative studies.

Ecosystem↗
PubMed2004

Biomorphometric analysis of human prostatic carcinoma by using three-dimensional computer models.

Advances in the detection of carcinoma of the prostate during the last 15 years have accounted for a sharp increase and then an abrupt decrease in the incidence of the disease. A more recent decline in its mortality rates has been variously interpreted as either the success of early detection and improved treatment or lead-time bias. The recently reported Prostate Cancer Prevention Trial had an overall detection rate that approached the 30%-40% prevalence rates reported in autopsy series in which men died of other causes. However, the prognostic information that can be obtained from prostate cancer found on biopsy is limited. Three-dimensional computer modeling is one technique that allows multiple studies on "immortal" prostates to test methods of biopsy sampling accuracy and to assist in the determination of the disease's severity. Computer modeling can assess detection rates and assesses tumor multifocality and heterogeneity. It can provide a more accurate representation of tumor volume, aiding in therapeutic decision making, and can assess sampling errors of various biopsy methods. It has been shown to be superior to wire-frame technique by immortalizing the original shape and dimensions of the surgically excised prostate gland. Moreover, our 3-dimensional computer modeling system improves upon other systems: It is more than a simple extension of the planimetric technique, and it is able to demarcate clearly the boundaries of Gleason grades just 1 grade apart.

Adenocarcinoma↗
PubMed2006

Low-dose prophylactic craniospinal radiotherapy for intracranial germinoma.

PURPOSE: To report outcomes of patients with localized intracranial germinoma treated with low-dose craniospinal irradiation (CSI) followed by a boost to the ventricular system and primary site. METHODS AND MATERIALS: Thirty-one patients had pathologically confirmed intracranial germinoma and no spine metastases. Low-dose CSI was administered in 29 patients: usually 21 Gy of CSI, 9.0 Gy of ventricular boost, and a 19.5-Gy tumor boost, all at 1.5 Gy per fraction. Our neuroradiologist recorded three-dimensional tumor size on magnetic resonance images before, during, and after radiotherapy. RESULTS: With a median follow-up of 7.0 years, 29 of 31 patients (94%) are disease free. One failure had nongerminomatous histology; the initial diagnosis was a sampling error. Of 3 patients who did not receive CSI, 1 died. No patient developed myelopathy, visual deficits, dementia, or skeletal growth problems. In locally controlled patients, tumor response according to magnetic resonance scan was nearly complete within 6 months after radiotherapy. CONCLUSIONS: Radiotherapy alone with low-dose prophylactic CSI cures almost all patients with localized intracranial germinoma. Complications are rare when the daily dose of radiotherapy is limited to 1.5 Gy and the total CSI dose to 21 Gy. Patients without a near-complete response to radiotherapy should undergo resection to rule out a nongerminomatous element.

Adolescent↗
PubMed2006

Is melanocytic nevus with focal atypical epithelioid components (clonal nevus) a superficial variant of deep penetrating nevus?

BACKGROUND: We compare features of two similar nevi which may be confused with melanoma: deep penetrating nevus (DPN), and nevus with focal atypical epithelioid component (NFAEC). METHODS: Clinical/demographic and histologic information regarding 146 DPN and 81 NFAEC were compared. Patient outcomes were ascertained via a questionnaire solicited to the referring physicians. RESULTS: Clinical features were similar for each type of nevus. Histologically, all lesions demonstrated identical aggregates of epithelioid melanocytes. DPN more often extended into the deep dermis or subcutaneous tissue, while NFAEC was typically confined to the superficial dermis. NFAEC more often demonstrated a junctional component (P < .001) and coexistent common nevus with congenital features (P = .035). DPN more often demonstrated adnexal spread (P < .001). A subgroup with overlapping features was identified. With an average of 6.4 years follow-up, there were just two recurrences, and no metastases. LIMITATIONS: This retrospective study utilized tissue specimens from a single reference laboratory; ergo, some inherent selection bias exists. Specimens were randomly selected for P53 immunostaining, leading also to potential sampling error. CONCLUSIONS: DPN and NFAEC show considerable similarity, differing mainly in the depth of extent for the lesion. It is possible that NFAEC represents a more superficial variant of DPN. A subgroup with overlapping features, but intermediate depth, supports such a relationship.

Adolescent↗
PubMed2005

Tree disagreement: measuring and testing incongruence in phylogenies.

The branching patterns of phylogenetic trees often disagree even when they have been constructed using different portions of the same data. This phylogenetic discord (incongruence) can be explained by real differences in evolutionary process or history, but also may be due simply to random chance or sampling error. Techniques for measuring and testing the significance of phylogenetic incongruence are used widely in systematic biology, and are necessary when considering genome-scale datasets composed of multiple genes that may or may not have different histories. They are also applicable wherever tree algorithms are used for ordering and interpreting data (e.g., DNA microarrays). Here, I review the different incongruence tests and use them to test the phylogenetic discord of a potentially mobile genetic element (the widespread colonization Island) in the gamma-proteobacteria. I then consider how incongruence tests may be used as a starting point for phylogenetic analysis that accounts for horizontal transfer and duplication events as explanations for homoplasy.

Algorithms↗