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PubMed1979

Pathology: the evolution of a specialty in American medicine.

The historical evolution of pathology as a full-time specialty in medicine is viewed as a response of pathologists to changes in the level and pattern of demand for their services. The development and decline of morphologic pathology, changes in academic pathology and the evolution of clinical pathology from a medical specialty to an industry with an extensive division of labor are all examined in this perspective. It is shown that pathology as a medical specialty is most successful within a limited range of demand, neither too low to support full-time specialization nor too high to lead to deprofessionalization through routinization of the work activities of pathologists.

Health Services Needs and Demand↗
PubMed1997

Predictors of intracranial pathologic findings in patients who seek emergency care because of headache.

BACKGROUND: Clinical criteria to select patients with headache in whom structural diagnostic studies (computed tomography) have a high yield disclosing intracranial pathologic findings, independent of abnormal findings on neurologic examination, have not been defined. OBJECTIVE: To determine which clinical characteristics predict the presence of intracranial pathologic findings, independently of neurologic examination, in patients with headache. DESIGN: Case-control, consecutive sample. SETTING: Major metropolitan trauma center emergency department. PATIENTS AND MATERIALS: Hospital records of 139 hospitalized and 329 randomly selected patients from 1720 nonhospitalized adult patients, consecutively evaluated for headache in the emergency department, were reviewed. Demographic data, clinical characteristics of the headache, results of neurologic and physical examinations, and diagnostic radiologic and laboratory results were correlated with final diagnosis and outcome at 6 months after emergency department visit. DATA ANALYSIS: Nonparametric statistical analysis. RESULTS: Intracranial pathologic findings were found in 18 (3.8%) of 468 patients. Acute onset and occipitonuchal location of headache, presence of associated symptoms, and patient age of 55 years or older were significantly associated with the finding of intracranial pathology, independently of the findings from neurologic examination. Abnormal findings on neurologic examination alone, whether focal or nonfocal, had a highly significant association and a positive predictive value for intracranial pathology of 39%. CONCLUSIONS: Abnormal results from neurologic examination are the best clinical parameters to predict structural intracranial pathology; however, in patients 55 years or older with headache of acute onset located in the occipitonuchal region that has associated symptoms, computed tomographic scan of the head is justified as part of their clinical evaluation independently of the findings of the neurologic examination.

Adult↗
PubMed1999

Clinical and pathological evidence for a frontal variant of Alzheimer disease.

OBJECTIVE: To evaluate the clinical and pathological features of a subgroup of patients with Alzheimer disease (AD) who exhibited early and disproportionately severe impairments on tests of frontal lobe functioning. We hypothesized that these patients would exhibit a greater degree of either neurofibrillary tangle (NFT) or senile plaque pathology in the frontal lobes than would patients with typical AD. DESIGN AND OUTCOME MEASURES: We examined the neuropsychological profiles and senile plaque and NFT accumulation in the frontal, entorhinal, temporal, and parietal cortices in 3 patients with AD who exhibited disproportionate frontal impairments during early stages of dementia (frontal AD) and 3 matched patients with typical AD (typical AD). RESULTS: Compared with the typical AD group, the frontal AD group performed significantly worse on 2 tests of frontal lobe functioning and on the Wechsler Adult Intelligence Scale-Revised Block Design test. No significant group differences were found on other tests. Analysis of brain tissue samples demonstrated that, despite comparable entorhinal, temporal, and parietal NFT loads, the frontal AD group showed a significantly higher NFT load in the frontal cortex than the typical AD group. Senile plaque pathology in the frontal and entorhinal cortices did not differentiate the 2 groups. CONCLUSIONS: We identified a subgroup of patients with pathologically confirmed AD who presented in the early stages of dementia with disproportionate impairments on tests of frontal lobe functioning and had a greater-than-expected degree of NFT pathology in the frontal lobes, suggesting the existence of a frontal variant of AD that has distinctive clinical and pathological features.

Aged↗
PubMed2005

Effect of genes, environment, and lifetime co-occurring disorders on health-related quality of life in problem and pathological gamblers.

BACKGROUND: Problem and pathological gambling are associated with many impairments in quality of life, including financial, family, legal, and social problems. Gambling disorders commonly co-occur with other psychiatric disorders, such as alcoholism and depression. Although these consequences and correlates have been reported, little is known about the health-related functional impairment associated with gambling. OBJECTIVE: To model differences in the health-related quality of life (HRQoL) among non-problem gamblers, problem gamblers, and pathological gamblers after controlling for lifetime co-occurring substance use disorders, psychiatric disorders, sociodemographics, and genetic and family environmental influences. DESIGN: Cohort and co-twin studies. SETTING: Nationally distributed community sample. PATIENTS: Male twin members of the Vietnam Era Twin Registry: 53 pathological gamblers, 270 subclinical problem gamblers, and 1346 non-problem gamblers (controls). INTERVENTIONS: We obtained HRQoL data, via the 8-Item Short-Form Health Survey, from all participants. Data from a subset of twin pairs discordant for gambling behavior was used to control for genetic and family environmental effects on HRQoL and problem gambling. Main Outcome Measure Health-related quality of life. RESULTS: Results from adjusted logistic regression analyses suggest little difference across groups in the physical domains of the health survey; however, for each mental health domain, pathological gamblers had lower HRQoL scores than problem gamblers (P<.05), who in turn had lower scores than non-problem gamblers (P<.05). After controlling for genes and family environment, no significant differences existed between the non-problem gambling twins and their problem or pathological gambling brothers, but adjusted co-twin analyses resulted in statistically significant differences in 4 of 8 subscales. CONCLUSIONS: Pathological and problem gambling are associated with significant decrements in HRQoL. This association is partly explained by genetic and family environmental effects and by lifetime co-occurring substance use disorders. Implications for clinicians, health care utilization, and public health issues are discussed.

Cohort Studies↗
PubMed1996

Pathologic staging of prostate carcinoma. What are the issues?

BACKGROUND: Stage is a significant predictor of outcome for patients with carcinoma of the prostate. The American Joint Committee on Cancer (AJCC) and the International Union Against Cancer (UICC) TNM staging system has gained general favor as the clinical staging system of choice for prostate carcinoma. With an increasing number of publications assessing prognostic markers for patients with carcinoma of the prostate, there is a need for the development of a uniform system of pathologic staging to support the clinical stage. METHODS: The literature related to pathologic prognostic markers for patients with carcinoma of the prostate, particularly with regard to staging, was reviewed. From this, issues important to the development of a pathologic correlate to the AJCC/ UICC TNM system were identified. RESULTS: A number of issues were identified related to the development of a pathologic staging system. For radical prostatectomy specimens some of the more important are whether or not subcategorization is needed in the pathologic classification of T2 tumors, definition and quantification of extraprostatic extension, and the reporting of positive surgical margins. CONCLUSIONS: There is a need for the development of a pathologic equivalent to the AJCC/UICC TNM clinical staging system for prostate carcinoma. Consensus needs to be reached on several important issues prior to the adoption and testing of such a system.

Carcinoma↗
PubMed1998

Biological markers as indicators of pathological response to primary chemotherapy in oral-cavity cancers.

The predictive role in terms of pathological response and prognostic role of biomarkers such as GST-pi, p53, bcl-2 and bax expression, immuno-histochemically detected, and of the S-phase cell fraction, autoradiographically determined as thymidine labeling index (TLI), were investigated within a prospective randomized phase III clinical trial on squamous-cell carcinoma of the oral cavity, including surgery or primary chemotherapy (PCT), which foresaw the prospective determination of biological markers. Pathological response was defined as the achievement after PCT of a pathological complete remission or the presence of microresidual disease. The study was performed on tumors obtained from a series of 100 previously untreated patients with resectable T2-4N0-2M0 carcinoma. All biomarkers were unrelated, except for an inverse relation between TLI and GST-pi and a direct relation between bcl-2 and bax expression. In patients treated with surgery alone, 3-year disease-free survival (DFS) appeared to be weakly, but not significantly, related only to GST-pi and p53 expression. In patients treated with PCT, pathological response and DFS were independent of p53 expression and cell proliferation. Conversely, low GST-pi and bax expression were indicative of pathological response but lost relevance as predictors of DFS, whereas absence of bcl-2 was associated with high probability of 3-year DFS in the overall series as well as in non-responding patients. Within this latter sub-set, all patients with bcl-2-positive tumors relapsed within 1 year of surgery, whereas a 60% probability of 3-year DFS was observed for patients with bcl-2-negative tumors (p = 0.02). This interim analysis appears to indicate that some biofunctional markers can provide information on pathological response to PCT and could help in understanding treatment efficacy at a cellular level.

Biomarkers↗
PubMed1987

Pathologic fracture in osteosarcoma. Impact of chemotherapy on primary tumor and survival.

Twenty patients with osteosarcoma and pathologic fractures were treated with a chemotherapeutic regimen consisting of cis-diamminedichloroplatinum-II (CDP), Adriamycin (ADR) (doxorubicin) and high-dose methotrexate with citrovorum factor "rescue" (MTX-CF). Before the introduction of the regimen, the primary tumor in two patients was treated by immediate amputation and in 13 with preoperative intra-arterial CDP. Among these 13 patients, responses (healing) were observed in 11 (one required the addition of radiation therapy). In three patients, the responses were so dramatic that, at their request, surgery was deferred and treatment exclusively with chemotherapy was instituted. Based on this experience, treatment exclusively with chemotherapy was also administered to an additional five patients who were admitted without pathologic fractures. In the course of such treatment, pathologic fractures also developed; notwithstanding, chemotherapy was maintained and healing also occurred. One of the 20 patients had pulmonary metastases at diagnosis; these were resected after treatment and pathologic examination revealed no evidence of viable tumor. The remaining 19 patients were free of pulmonary metastases but these later developed in seven patients. These data were compared to a historical control series in which 16 of 21 patients with pathologic fractures developed pulmonary metastases. Three of the chemotherapy treated patients died of nonosteosarcoma related causes (leukemia, generalized varicella, and a metabolic complication). Overall, survival was improved in the chemotherapy treated patients as compared to the historical control series: 10 of 20 versus 6 of 21, respectively. Pathologic fractures in osteosarcoma may heal under treatment with chemotherapy, which also has a favorable impact on the eradication of pulmonary metastases and survival.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Stratification of pathologic features in radical prostatectomy specimens that are predictive of elevated initial postoperative serum prostate-specific antigen levels.

BACKGROUND: Prostate-specific antigen (PSA) is an important marker for adenocarcinoma of the prostate and is of clinical utility in assessment of residual carcinoma after radical prostatectomy. Although elevated postoperative serum PSA levels have been linked to pathologic stage in radical prostatectomy specimens, limited data are available on the relationship of postoperative PSA levels to margin positivity, intraglandular tumor extent, and histologic grade. METHODS: Initial postoperative serum PSA levels were related to pathologic features of 90 radical prostatectomy specimens with adenocarcinoma of the prostate. Logistic regression analysis was used to stratify pathologic stage, percentage intraglandular carcinoma, histologic grade, and margin positivity as predictors of elevated initial postoperative PSA levels. RESULTS: Pathologic stage, percentage carcinoma, and margin positivity were nearly equivalent in strength of prediction, whereas Gleason histologic grade was a significant but less reliable predictor of elevated initial postoperative PSA levels. Thirty-one of 51 (60.8%) patients with extension of carcinoma outside the prostate gland had an elevated initial postoperative PSA level, whereas only 5 of 39 (12.8%) patients with organ-confined carcinoma had an elevated postoperative PSA level. Intraglandular tumor extent greater than 10% was associated with a greater likelihood of an elevated postoperative PSA level. Additional predictive capacity was obtained with concurrent use of pathologic stage and percentage carcinoma or margin positivity in multivariate analysis. CONCLUSIONS: In radical prostatectomy specimens, pathologic stage, intraglandular carcinoma extent, and margin positivity are particularly important morphologic parameters because they are predictive of residual carcinoma that is detected early, as judged by an elevated initial postoperative serum PSA level.

Adenocarcinoma↗
PubMed1993

The value of pathologic factors in predicting cancer-specific survival among patients treated with radical cystectomy for transitional cell carcinoma of the bladder and prostate.

BACKGROUND: A recent consensus conference on bladder carcinoma highlighted the need for pathologic predictors of outcome for patients with transitional cell carcinoma of the bladder. This review was undertaken to determine the pathologic features predictive of cancer-specific survival after a radical cystectomy and urinary diversion for transitional cell carcinoma of the bladder and prostate. METHODS: Between 1969 and 1990, 531 patients with transitional cell carcinoma of the bladder and prostate were treated with radical cystectomy at the Duke University Medical Center. Records and pathologic specimens were analyzed and correlated with outcome. Both univariate and multivariate analyses of the pathologic staging were performed to identify variables predictive of cancer-specific survival. RESULTS: Univariate analysis indicated that pathologic tumor (pT) stage, positive nodes, positive surgical margins, prostatic stromal involvement, grade, age, ureteral involvement, squamous cell carcinoma, and squamous cell differentiation in the specimen all were predictive of poor cancer-specific survival. Carcinoma in situ (CIS) in the specimen was not an adverse prognostic indicator. Multivariate analysis demonstrated that the pT stage, nodal involvement, positive surgical margins, patient's age at surgery, and loss of histologic differentiation were predictive of poor cancer-specific survival. CIS was found again not to have a negative influence on cancer-specific survival. CONCLUSIONS: If any of these features are noted in the final pathologic specimen, patients should be considered for some form of additional postoperative treatment such as chemotherapy or radiation therapy in an attempt to improve their chances for cancer-free survival. These factors will become more important in selecting which patients should be placed in developing adjuvant clinical trials.

Adult↗
PubMed1995

Central pathology review in clinical trials for patients with malignant glioma. A Report of Radiation Therapy Oncology Group 83-02.

BACKGROUND: Confounding biologic factors, including histologic grade, may influence the outcome of adult patients with malignant gliomas more than may modifications in therapeutic approach. Any clinical trial design for malignant gliomas in adults must account for such biologic factors, including the accurate identification of the two histologic subgroups astrocytoma with anaplastic foci (AAF) or glioblastoma multiforme (GBM), which are associated with distinctly different survival outcomes. This paper examines the need for a central pathology review before entry of patients in cooperative group clinical trials stratified by histologic grade. METHODS: Pathology slides from Radiation Therapy Oncology Group (RTOG) trial 83-02, a randomized Phase II study of hyperfractionated and accelerated hyperfractionated radiation therapy and carmustine for malignant gliomas, provided 747 analyzable cases, with 680 (91%) available for central pathology review. This review was performed by a single pathologist according to RTOG/Eastern Cooperative Oncology Group histopathologic criteria. The kappa statistic was used to measure agreement between the institutional and central classification of AAF and GBM. The influence of misclassification was examined using computer simulation of varying clinical trial sizes (n = 25, 50, or 200). The effect on the statistical power of trials (n = 200) with varying mixtures of AAF and GBM tumors was investigated using computer simulations. RESULTS: Of 159 tumors classified as AAF by institutional pathology review, only 66% (105) were classified as AAF (AAF/AAF) by central review, and 54 of these cases (34%) were classified as GBM (GBM/AAF), whereas 96% (501) of 521 institutionally classified as GBM (GBM/GBM) were similarly classified by central review. Computer simulations demonstrated a 59% underestimation in the median survival (1.82 vs. 4.49 years) for trials of patients with institutionally defined AAF compared to patients with centrally defined AAF in studies of 200 patients, resulting from the addition of poor prognosis of GBM in the trial. Misclassification can also substantially reduce the statistical power of a clinical trial. In one of the simulation studies, statistical power was reduced from 65% to 14% if 50% of the patients were to receive an inaccurate histologic classification. Even greater losses in power are possible in many plausible clinical settings. CONCLUSIONS: This examination of a central versus an institutional pathology review demonstrates a low level of agreement on AAF classification and a high level of concordance on GBM classification. The results indicate the need to adjust sample size for trials of both AAF and GBM tumors to have adequate statistical power. A central pathology review remains essential for trial entry for patients with AAF and could be omitted for trials enrolling patients with GBM only.

Adult↗
PubMed2001

Breast carcinomas of limited extent: frequency, radiologic-pathologic characteristics, and surgical margin requirements.

BACKGROUND: Clinical trials established the value of breast-conserving treatment (BCT) including the macroscopic removal of the tumor followed by local radiation therapy (RT) for Stage I and II invasive carcinomas. The occurrence of local tumor recurrence is related to the extent and multifocality of the tumor. Various studies aim to identify those tumors that could be proper candidates for conventional BCT. Furthermore, recent studies have focused on the identification of tumors that may be treated by breast-conserving surgery alone without RT. Small, localized tumors theoretically should be the potential candidates for this type of treatment. The mammographic and pathologic criteria for the identification of tumors with limited extent are not yet established; furthermore, the optimal extent of the surgical excision and the method for margin examination are controversial. METHODS: Surgical breast-conserving procedures were simulated in a review of 135 mastectomy specimens of patients treated for an invasive carcinoma (> or = 4 cm in size, all pathologic types except invasive lobular carcinoma) who were theoretically eligible for conservative treatment. Tumor spread including possible multifocality and multicentricity was studied by the technique of correlated specimen radiography and pathology. Breast carcinoma of limited extent (BCLE), the proper tumor profile for BCT, was defined as having no invasive carcinoma, ductal carcinoma in situ, and lymphatic emboli foci beyond 1 cm from the edge of the dominant mass. RESULTS: Fifty-three percent of the patients in this series had a BCLE. No statistically significant relation was found between BCLE and patient age, pathologic size, type and grade of the tumor, lymph node status, mode of detection, and mammographic aspect of the index tumor. Based on mammography, the absence of calcification or tumor density beyond the edge of index tumor appears to be the best predictor for BCLE (P < 0.0001). A 1-cm microscopically tumor free margin as the outer rim of a macroscopic surgical margin of 2 cm gives the best positive predictive value based on pathology (P < 0.0001). By applying the above conditions, 72 of the 135 cancers were identified as being potential BCLE cases in this series. However, whereas 64 of these 72 tumors (89%) were correctly identified as being true BCLE, 8 (11%) were erroneously identified as such (non-BCLE cases), having "residual" tumor foci beyond 2 cm from the edge of the dominant tumor. CONCLUSIONS: We conclude, that approximately 50% of invasive ductal carcinomas may have limited extent. The accuracy of identifying this group of cancers, the proper candidates for BCT, by applying state-of-the-art mammography and pathology may be as high as 90%. A subset of these tumors might represent the potential candidates for treatment with surgery alone without RT. As a result, the routine application of BCT complemented by RT would have led to the overtreatment of 89% of the patients with a BCLE in this series; conversely, 11% of the tumors may have recurred without the use of RT. Considering that these conclusions are based on a theoretic morphologic model, further clinical studies with facilities for high quality team approach in diagnosis and therapy are needed to evaluate the impact of BCLE on BCT strategies. The results of this study should not justify the withholding of RT outside the context of clinical trials.

Breast Neoplasms↗
PubMed1995

Dental pathology in Pongo satyrus borneensis.

The Selenka orangutan collection obtained from 1892 to 1896 from wild-shot specimens in West Borneo, provides an excellent opportunity to examine dental pathology in free-ranging primates. Two hundred and twenty-three skulls from this collection were analyzed for dental conditions, including carious lesions, local infections (infra-alveolar and periapical osseous defects), horizontal bone loss, and premortem tooth loss. Specimens were sexed, divided into three broad age groups, and compared to ascertain sex-related or age-related differences in occurrence of dental pathology. None of the subadults displays any evidence of dental disease. One individual (2%) in the young adult group has a periapical osseous defect and evidence of horizontal bone loss, and another (2%) has two adjacent interproximal carious lesions. The old adults have a much higher prevalence of individuals afflicted with dental pathologies, including 6% carious lesions, 26% local infections, 23% horizontal bone loss, and 3% premortem tooth loss. The differences between the young and old adults in number of individuals afflicted with dental pathologies is statistically significant for local infections and horizontal bone loss. When compared by sex, the old adult group reveals that females have a higher occurrence of dental pathologies than males in all types of lesions recorded and these differences are statistically significant for local infections and horizontal bone loss. Considering the importance diet plays in the development of dental disease, it is suggested that ecological separation of the sexes, with the subsequent dietary differences, could be an important factor determining the higher prevalence of dental lesions observed in female orangutans. Additionally, the importance of local ecological factors, which may affect dietary patterns, are recognized as a potential source of variation in dental pathologies among different samples of orangutans.

Age Factors↗
PubMed2006

Unexpected abundance of pathological tau in progressive supranuclear palsy white matter.

OBJECTIVE: To investigate whether biochemical insoluble tau with 4 (4R) and/or 3 (3R) microtubule-binding repeats accumulate in white as well as gray matter in progressive supranuclear palsy (PSP), a neurodegenerative tauopathy. METHODS: To assess tau pathology in PSP white matter, we combined Western blot (WB) and immunohistochemical methods to analyze 23 autopsy-confirmed PSP brains. RESULTS: WBs showed an unexpected abundance of insoluble tau in white and gray matter of PSP brains, but biochemical tau pathology in white matter was not correlated with immunohistochemistry using the same panel of epitope-specific anti-tau antibodies used for WB. Despite heterogeneity in the representation of pathological 3R and 4R tau isoforms in cortical versus subcortical regions, biochemically detectable white matter tau pathology is a constant feature of PSP. INTERPRETATION: These studies show additional similarities between PSP and corticobasal degeneration, but unlike corticobasal degeneration, more abundant white matter tau pathology in PSP is detectable by WB than by immunohistochemistry. The differential detection of abnormal tau by biochemistry versus microscopy in PSP may reflect distinct pathological mechanisms, and elucidation of these processes will augment efforts to develop better strategies for the diagnosis and treatment of PSP and related neurodegenerative tauopathies.

Aged↗
PubMed2006

Cognitive impact of subcortical vascular and Alzheimer's disease pathology.

OBJECTIVE: To assess the interactions among three types of pathology (ie, cerebrovascular disease, hippocampal sclerosis [HS], and Alzheimer's disease [AD]), cognitive status, and apolipoprotein E genotype. METHODS: We report clinicopathological correlations from 79 autopsy cases derived from a prospective longitudinal study of subcortical ischemic vascular disease and AD. RESULTS: Thirty percent of the cases had significant cerebrovascular parenchymal pathology scores (CVDPS), 54% had significant AD pathology, and 18% had HS. In an ordinal logistic regression analysis that included interaction terms to assess the effects of each pathological variable when the other variables are interpolated to zero, each of the three pathology variables contributed independently to cognitive status: Braak and Braak stage odds ratio (OR) = 2.84 (95% confidence interval, 1.81-4.45), HS score OR = 2.43 (95% confidence interval, 1.01-5.85), and CVDPS OR = 1.02 (95% confidence interval, 1.00-1.04). Only Braak and Braak stage contributed to a global neuropsychological measure of cognitive impairment. Apolipoprotein E4 genotype was associated with Braak and Braak stage (OR, 1.31 [95% confidence interval, 1.03-1.68]), but not CVDPS or HS scores. INTERPRETATION: In this convenience sample enriched for subcortical ischemic vascular disease, HS was a common unsuspected neuropathological finding. Apolipoprotein E4 genotype was associated with cerebral amyloid angiopathy, but not HS or arteriosclerosis. When Braak and Braak stage was interpolated to zero, both CVDPS and HS contributed to cognitive impairment. However, advancing stages of AD pathology overwhelmed the effects of CVDPS and HS, to become the major determinant of dementia.

Aged↗
PubMed1982

Pathological findings underlying focal temporal lobe hypometabolism in partial epilepsy.

Histopathological studies were carried out on temporal lobe tissue from 25 patients with partial complex seizures who were studied by interictal positron computed tomography (PCT) with 18F-fluorodeoxyglucose and subsequently underwent anterior temporal lobe resection. Abnormalities were identified on x-ray computed tomographic scans in 7 patients, but none indicated the site of a pathologically confirmed structural lesion. Hypometabolic zones were observed on PCT scans of 22 patients and corresponded to focal pathological abnormalities in 19 (15 mesial temporal sclerosis, 2 small neoplasms, 1 angioma, 1 heterotopia). In 1 patient with a focally abnormal PCT scan and no pathological changes, the lesion may have been located posterior to the resection. In the remaining 2 patients, the hypometabolic zones later disappeared and may have represented a transient response induced by depth electrode implantation. Three patients with normal PCT scans had no pathological abnormalities in their resected tissue. The degree of relative hypometabolism measured by PCT correlated well with the severity of the pathological lesion, but the size of the hypometabolic zone was generally much larger than the area of pathological involvement. This discrepancy could not be considered an artifact of technique and must represent either structural abnormalities below the resolution of routine histopathological studies (e.g., loss of synapses) or functional inactivation of neuronal elements associated with the epileptogenic lesion.

Adolescent↗
PubMed1997

Doppler echocardiography distinguishes between physiologic and pathologic "silent" mitral regurgitation in patients with rheumatic fever.

BACKGROUND: The diagnosis of rheumatic fever is based on physical findings (major) and supporting laboratory evidence (minor) as defined by the Jones criteria. Rheumatic carditis is characterized by auscultation of a mitral regurgitant murmur. Doppler echocardiography, however, may detect mitral regurgitation when there is no murmur ("silent" mitral regurgitation), even in normal individuals. HYPOTHESIS: The hypothesis of this study was that physiologic mitral regurgitation can be differentiated from pathologic "silent" mitral regurgitation by Doppler echocardiography. METHODS: The study group consisted of 68 patients (2-27 years) with normal two-dimensional imaging and Doppler evidence of mitral regurgitation but no murmur. Patients with rheumatic fever (n = 37) met Jones criteria (chorea in 20, arthritis in 17). Patients without rheumatic fever (n = 31) were referred for innocent murmur (n = 7), abnormal electrocardiogram (n = 13), and chest pain (n = 11). Echoes were independently reviewed by two cardiologists blinded to the diagnosis. Pathologic mitral regurgitation was defined as meeting the following four criteria: (1) length of color jet > 1 cm, (2) color jet identified in at least two planes, (3) mosaic color jet, and (4) persistence of the jet throughout systole. Jet orientation was also noted. RESULTS: Using the above criteria, there was agreement in echo interpretation of pathologic versus physiologic mitral regurgitation in 67 of 68 patients (interobserver variability of 1.5%). Pathologic regurgitation was found in 25 (68%) patients with rheumatic fever but in only 2 (6.5%) patients without rheumatic fever (p < 0.001). The specificity of Doppler for detecting pathologic regurgitation was 94% with a positive predictive value of 93%. The color mitral regurgitant jet was posteriorly directed in all 25 patients with rheumatic fever. CONCLUSION: Pathologic "silent" mitral regurgitation of rheumatic fever can be distinguished from physiologic mitral regurgitation using strict Doppler criteria, particularly when the jet is directed posteriorly. These data support the use of Doppler echocardiography as a minor criterion for evaluating patients with suspected rheumatic fever.

Acute Disease↗
PubMed2005

Posttherapy pathologic stage predicts survival in patients with esophageal carcinoma receiving preoperative chemoradiation.

BACKGROUND: In patients with locoregional carcinoma of the esophagus or esophagogastric junction who underwent preoperative chemoradiation, it is unclear whether survival was better predicted by pretherapy clinical stage or by posttherapy pathologic stage. METHODS: The authors studied 235 consecutive patients with pretherapy clinical Stage II, III, or IVA (according to American Joint Committee on Cancer criteria) carcinoma of the esophagus or esophagogastric junction who were treated with chemoradiation followed by esophagectomy. Posttherapy cancer status was classified using pathologic stage and semiquantitative assessment of residual carcinoma. Clinicopathologic features, residual carcinoma status, and pretherapy and posttherapy stage were compared with disease-free and overall survival. RESULTS: Posttherapy pathologic stage was Stage 0 in 29% of patients, Stage I in 11% of patients, Stage II in 34% of patients, Stage III in 20% of patients, and Stage IV in 6% of patients. Cancer downstaging occurred in 56% of patients. In univariate analysis, disease-free and overall survival were predicted by posttherapy pathologic stage (both with P < 0.001), margin status (P = 0.002 and P = 0.01, respectively), extent of residual carcinoma (both with P < 0.001), and downstaging (both with P = 0.001), but not by age, gender, type of cancer, pretherapy clinical stage, or preoperative regimen. However, in multivariate analysis, disease-free and overall survival were independently predicted by posttherapy pathologic stage (both with P = 0.02). Extent of residual carcinoma was a marginally significant predictor of overall survival (P = 0.04). CONCLUSIONS: Posttherapy pathologic stage was the best available predictor of outcome for patients with locoregional carcinoma of the esophagus or esophagogastric junction who underwent chemoradiation therapy followed by esophagectomy. The findings in the current study supported the concept of downstaging by preoperative therapy.

Carcinoma↗
PubMed2006

Pathologic findings from the Breast Cancer Surveillance Consortium: population-based outcomes in women undergoing biopsy after screening mammography.

BACKGROUND: To the authors' knowledge, a comprehensive analysis of pathology outcomes after screening mammography, as it is practiced clinically in the U.S. general population, has not been performed. METHODS: Breast Cancer Surveillance Consortium data from 1996-2001 were used to identify pathology specimens that were obtained within 1 year of screening mammograms performed on 786,846 women ages 40-89 years. The pathology results were classified as invasive carcinoma, ductal carcinoma in situ (DCIS), or benign. The associations between overall pathology outcomes and invasive tumor size and lymph node status were analyzed by age and mammography assessment category. RESULTS: The rates of both recommending and performing a biopsy varied little with age. The 1,664,032 screening mammograms were followed by 26,748 known biopsies (1.6%) and 8815 diagnoses of breast carcinoma (0.53%). Overall, 81% of carcinomas were invasive, and 78% of those were pathologically lymph node-negative tumors, in contrast to the 66% prevalence observed in the Surveillance, Epidemiology, and End Results (SEER) data during the same period. Most invasive tumors measured between 0 mm and 10 mm (35%) or between 11 mm and 20 mm (36%) in greatest dimension, and 92% and 78% were lymph node-negative tumors, respectively: Biopsy results that were classified as malignant increased with age (P < 0.0001) and were most likely to follow Breast Imaging, Reporting, and Diagnosis System Category 5 and 4 assessments, respectively. Ductal hyperplasia (19.6%), fibroadenoma (18.5%), and other benign findings (56.1%) were the most common benign diagnoses. CONCLUSIONS: Pathologically negative lymph nodes were more prevalent in this mammographically screened population than in the overall SEER population. The prevalence of invasive carcinoma, DCIS, and benign findings presented herein establish a range of expected biopsy outcomes for women after screening mammography in the general U.S. population.

Adult↗