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PubMedDate not supplied

Investigation of biotransformation capacity in patients with chronic liver diseases by pharmacokinetic methods: experimental trials.

The drug metabolizing capacity of patients with liver disease varies with the characteristics and the state of the disease. The aim of our studies on patients with various chronic liver diseases was to get information about the rational dosage for these patients. Our method in the first phase was antipyrine kinetics (hydroxylation), in the second phase sulfadimidine kinetics (acetylation) and menthol loading (glucuronidation). The induced state was investigated by D-glucaric acid excretion. Experimental trials: 1) comparison of groups of patients with moderate and severe liver diseases with each other, or with the normal control (two sample t test); 2) comparison of various groups of patients with each other and with the normal control (variance analysis); 3) research of potential correlation between the kinetic and biochemical parameters (correlation analysis); 4) reclassification studies with the use of kinetic and biochemical parameters (discrimination analysis). We discuss the practical advantage of the various experimental trials. The most important conclusion is that the reclassification by discrimination analysis gives important data to the economic planning of experiments.

Antipyrine↗
PubMed2026

Additive value of polygenic risk and family history for coronary heart disease risk stratification in two diverse US cohorts.

Whether polygenic risk, monogenic familial hypercholesterolemia (FH), and family history (FamHx) are additively informative for coronary heart disease (CHD) risk prediction across self-identified race/ethnicity (SIRE) groups has not been established. In two diverse cohorts-Electronic Medical Records and Genomics (eMERGE) phase IV (eIV; n = 19,348) and All of Us (AoU; n = 239,645)-we quantified the associations of a polygenic risk score (PRSCHD), pathogenic/likely pathogenic variants in genes associated with FH, and FamHx with CHD and evaluated their incremental value when added to the pooled cohort equations (PCEs). CHD was defined as myocardial infarction, unstable angina, or coronary revascularization. We modeled associations with multivariable logistic regression (prevalent CHD in eIV) and Cox proportional hazards (incident CHD in AoU) and characterized predictive performance with the c-statistic and reclassification and decision-curve net benefits across actionable 10-year risk thresholds. The effects of PRSCHD and FamHx were independent and additive in both cohorts and consistent across White, Black, and Latino SIRE groups. In eIV, adding PRSCHD and FamHx to the PCE increased the c-statistic for prevalent CHD from 0.719 to 0.753 (p-diff = 9.1 × 10-3) and reclassified 18.8% of participants at the 7.5% 10-year threshold, yielding approximately 4 additional true-positive CHD identifications per 1,000 screened. Net benefit gains were observed between the 7.5% and 10% thresholds across all three SIRE groups. In conclusion, PRSCHD and FamHx were independently and additively associated with CHD across major SIRE groups in two diverse cohorts in the United States (US), motivating the addition of these factors to clinical risk algorithms.

Humans↗
PubMed1999

Corneal thickness in ocular hypertension, primary open-angle glaucoma, and normal tension glaucoma.

OBJECTIVES: To determine the effect of central corneal thickness (CCT) on the measurement of intraocular pressure (IOP) and on the resultant reclassification of patients as having primary open-angle glaucoma (POAG), normal tension glaucoma (NTG), or ocular hypertension (OHT). METHODS: Intraocular pressure (Goldmann applanation tonomety) and CCT (ultrasound pachymetry) were measured in 22 patients with NTG, 49 with POAG, 44 with OHT and in 18 control subjects. The CCT was used to obtain a corrected value for the IOP and to reclassify the type of glaucoma. RESULTS: There was no significant difference in CCT between controls (552 +/- 35 microns) and patients with POAG (543 +/- 35 microns), but the CCT in the group with NTG (521 +/- 31 microns) was significantly lower than that in the control group or the group with POAG (P < .001), and the CCT in the group with OHT (583 +/- 34 microns) was significantly higher than in controls or patients with POAG (P < .001). Correcting IOP for corneal thickness, 31% of the patients with NTG could be reclassified as having POAG, and 56% of the patients with OHT as normal. CONCLUSIONS: Patients with NTG have a thinner CCT than do patients with POAG or controls. Underestimation of the IOP in patients with POAG who have thin corneas may lead to a misdiagnosis of NTG, while overestimation of the IOP in normal subjects who have thick corneas may lead to a misdiagnosis of OHT.

Aged↗
PubMed1990

The papillary-cystic neoplasm of the pancreas. An increasingly recognized clinicopathologic entity.

The clinical course of the papillary-cystic neoplasm of the pancreas is contrasted with that of the pancreatic ductal adenocarcinoma. The former occurs predominantly in young women, has a low malignant potential, and is highly curable with surgical treatment. Three cases are reported that illustrate the typical clinical features and the indolent nature of the tumor. One case was discovered after blunt abdominal trauma resulted in rupture of the tumor and hemoperitoneum. All cases were treated by pancreatic resection with preservation of the spleen, an important consideration in younger patients. All patients were free of disease at long-term follow-up. Increasing awareness of this tumor has resulted in the reclassification of several tumors and should lead to better recognition by surgeons caring for patients with pancreatic diseases.

Adolescent↗
PubMed1996

Histologic trends in thyroid cancer 1969-1993: a clinico-pathologic analysis of the relative proportion of anaplastic carcinoma of the thyroid.

BACKGROUND: It was observed that new presentations of anaplastic carcinoma of the thyroid had become infrequent in the last two decades. METHODS: All cases of thyroid cancer seen at our centre between 1969-1993 (n = 2921) were classified as papillary 49%, follicular 34%, medullary 7.5%, anaplastic 4.7%, and other 4.8%. The total number of thyroid cancers show a 3.5-fold rise. RESULTS: The differentiated thyroid cancers show a significant rising trend as against the relative proportion of anaplastic carcinoma, which shows a significant decline (P = 0.002). Clinicopathologic data on 124 patients of anaplastic carcinoma revealed 50% patients had either long-standing goitres, previous thyroid abnormalities, or associated differentiated thyroid carcinoma on histology. CONCLUSIONS: The decline in the relative proportion of anaplastic carcinoma may in part be explained by the clinicopathologic findings or it may be attributed to histological reclassification.

Adult↗
PubMed1999

DNA-ploidy analysis correlates with the histogenetic classification of thymic epithelial tumours.

The ploidy values of the epithelial component were determined in a series of thymomas and organotypic thymic carcinomas using image cytometry and the results were compared with the histological tumour subtypes according to the histogenetic classification introduced by Marino, Müller Hermelink, and Kirchner (MMHK). Forty-six cases of thymic epithelial tumours were included in the study. After reclassification according to the MMHK classification, the distribution among the subtypes was as follows: three medullary, nine mixed type, five predominantly cortical (organoid), 16 cortical thymomas, and 13 well-differentiated thymic carcinomas. Single cell preparations were made from paraffin-embedded tumour tissue and stained according to Feulgen. Ploidy analysis was performed using an automated image analysis system. In five cases, DNA cytometry could not be performed, for technical reasons. The remaining 41 cases consisted of 11 diploid and 30 non-diploid tumours. The percentage of aneuploid tumours in the different subtypes increased from medullary (0 per cent) through mixed type (44.4 per cent), predominantly cortical (75 per cent), cortical (83.3 per cent) to well-differentiated thymic carcinomas (100 per cent). DNA-ploidy determination using image cytometry correlates with the concept of the MMHK classification of thymomas.

Humans↗
PubMed1998

Pathologic classification of prostate carcinoma: the impact of margin status.

BACKGROUND: A proposed pathologic (pTNM) classification system for prostate carcinoma was analyzed for its impact on survival outcome in the prostate specific antigen (PSA) era. The impact of margin status on the survival outcome of patients with otherwise organ-confined disease (i.e., without extraprostatic extension or seminal vesicle involvement) was assessed. METHODS: Among 5467 patients, the original pathologic classification was T2 in 2094 patients; those with evidence of positive margins, extraprostatic extension, or seminal vesicle involvement were initially classified as having pT3 disease (2920 patients) or pT4 residual disease (211 patients). According to the proposed pTNM system, 1512 patients for whom margin status was considered independent of T classification were reclassified. RESULTS: After reclassification, 803 specimens had been down-classified to pT2, resulting in 2932 (54%) with pT2N0 organ-confined disease and a margin positivity rate of 27%; originally, only 38% of patients had been classified as pT2N0. When the old and new classifications were compared, 5-year progression free survival to the combined endpoint of clinical and/or PSA progression (< or = 0.2 ng/mL) was 86% versus 84% and 70% versus 67% for disease classified as pT2N0 and pT3N0, respectively. Multivariate analysis assessed the effect of margin status on 2334 pT2N0 patients (classified according to the proposed pTNM system) who did not receive adjuvant therapy; adjustments were made for Gleason grade, preoperative PSA, and DNA ploidy. In this analysis, the relative risk (with 95% confidence interval) associated with positive margins was 1.65 (1.24-2.18); this was significant for the combined endpoint of clinical/PSA progression. The 5-year survival, free of clinical/PSA progression, was 86% for those without versus 75% for those with positive margins. CONCLUSIONS: This analysis supports the adoption of the proposed pTNM system, which will allow for uniform reporting of pathologic data on prostate carcinoma. For patients with organ-confined disease, positive margins are associated with higher rates of PSA progression. Accordingly, patients should be stratified based on margin positivity in addition to pT classification.

Humans↗
PubMed2000

Sonographic and pathologic findings in typical and atypical medullary carcinomas of the breast.

PURPOSE: We investigated whether there was a relationship between the sonographic and histologic appearances of medullary carcinomas of the breast to determine whether sonography is helpful in the differentiation of typical and atypical medullary carcinomas. METHODS: We retrospectively reviewed the histologic slides and sonograms of 20 patients who had been diagnosed with medullary carcinoma of the breast. We then classified the carcinomas as typical or atypical based on strict histologic criteria. We also evaluated the relationship between sonographic findings and the histologic reclassification. RESULTS: Eight (40%) of the 20 medullary carcinomas were classified as typical, and 12 (60%) were classified as atypical. On sonography, a smooth outline was visualized in 6 (75%) of the 8 typical medullary carcinomas but in none of the 12 atypical carcinomas. A jagged margin was sonographically visualized in 10 (83%) of the 12 atypical carcinomas, and a focal irregularity in the margin was visualized in 2 (17%) of the 12 atypical carcinomas. Four of the typical medullary carcinomas had posterior enhancement, and 9 of the atypical medullary carcinomas showed retrotumoral shadowing. The difference in tumor-margin regularity between typical and atypical medullary carcinomas was found to be statistically significant (p < 0.001) using the 2-tailed Fisher's exact test. CONCLUSIONS: To prevent overdiagnosis of medullary carcinoma, a thorough pathologic review of the entire tumor is recommended if sonography shows a jagged margin or a margin with focal irregularity.

Adult↗
PubMed1978

Lobular neoplasia (so-called lobular carcinoma in situ) of the breast.

In a review and reclassification of 5,560 benign epithelial lesions of the breast entered in the files of the Laboratory of Surgical Pathology at Columbia, we found 211 examples of the type of lobular proliferation occurring alone without co-existing infiltrating carcinoma, which we prefer to call lobular neoplasia, but which is generally referred to as noninfiltrating lobular carcinoma in situ. We regard this lesion as a separate distinctive pathological-clinical entity. These 211 cases are studied from a number of parameters, including the ages of the patients, the breast affected, the length of the follow-up, the interval between the initial diagnosis and the frank carcinoma which eventually developed in 17.1 percent of the patients. The relationship of microscopic qualitative and quantitative variations in the lobular neoplasia to subsequent carcinoma was studied; the variations were not found to have any value in predicting subsequent carcinoma. This study is unique in that we have data as to the frequency of a family history of carcinoma in a mother or sister, and also as to the occurrence of gross cystic disease in our patients with lobular neoplasia. We have determined the ratio between the observed and expected numbers of patients developing carcinoma in the several possible combinations of these three factors which predispose to carcinoma. We report that the predisposition is cumulative: in patients in whom all three predisposing factors were present the ratio of observed to expected risk of carcinoma was 13:8. We do not recommend mastectomy for lobular neoplasia, but only systematic follow-up by palpation of the patients' breasts every four months.

Adult↗
PubMed1979

A clinicopathologic study of orbital and adnexal non-Hodgkin's lymphoma.

An analysis of non-Hodgkin's lymphoma involving the orbital structures was performed at the University of Iowa between 1937 and 1975. Sixteen cases of primary orbital lymphoma were diagnosed. Histopathologic reclassification according to the Rappaport scheme and the clinical course of each histologic sub-category was described. There were 5 patients with reactive hyperplasia, 2 patients with well-differentiated lymphoid proliferation with Dutcher bodies which were also felt to be reactive, 3 patients with diffuse poorly differentiated lymphocytic lymphoma, 4 patients with nodular poorly differentiated lymphocytic lymphoma, and 2 patients with diffuse histiocytic lymphoma. It was concluded that the Rappaport classification is applicable to orbital lymphoid tumors and that those lymphomas which do present as primary tumors should be staged as one would stage the same histologic category of lymphoma presenting in other sites. Radiation therapy appears to be an effective treatment for local control; however, patients with primary orbital lymphoma should undergo observation for systemic disease similar to patients with lymphoma presenting in other sites. Excisional biopsy is recommended to facilitate precise classification.

Aged↗
PubMed1990

Brain tumors in childhood and adolescence in west Sweden 1970-1984. Epidemiology and survival.

A population-based series of 198 children, aged 0 to 16.9 years, with primary brain tumors, diagnosed from 1970 to 1984, was retrieved from the Swedish Cancer Registry. After review of slides and reclassification of histology according to the American Cancer Society, the average annual incidence rate was estimated to be 34.9 per million, which is a very high incidence compared to other countries. The age distribution was not uniform as age group 0 to 4 included more children than age groups 5 to 9 and 10 to 14. The largest subgroups were astrocytomas (25%) and primitive neuroectodermal tumor (PNET)/medulloblastomas (MB) (21%). Associated diseases were neurofibromatosis and Rubinstein-Taybi syndrome. The overall male to female ratio was 1.08:1, the same as in the population at risk; but for PNET/MB, it was 1.8:1. The 5-year survival for all tumors was 54%, and the 15-year survival, 49%, with great variation between tumor subgroups.

Adolescent↗
PubMed1991

Comparison of S-phase fraction, working formulation, and Kiel classification in non-Hodgkin's lymphoma.

The prognostic value of S-phase fraction (SPF), determined by flow cytometric study from paraffin-embedded tissue, and grading by Working Formulation (WF) and Kiel classification were compared among 245 patients with non-Hodgkin's lymphoma followed for the median of 89 months or until death. Histologic reclassification and SPF determinations were done without knowledge on clinical data. SPF (P equals 0.0001), WF (P equals 0.0003), and Kiel classification (P equals 0.0008) were associated with mortality in lymphoma in a univariate analysis, and WF and SPF were independent prognostic factors in Cox's multivariate analysis. Although SPF correlated strongly both with WF and Kiel grades (P less than 0.0001), low-grade and high-grade malignant lymphomas according to Kiel classification, and high-grade lymphomas according to WF could be divided into groups with significantly different outcome by SPF. The results suggests a role for SPF in therapeutic decision-making.

Adolescent↗
PubMed1992

The new International Federation of Gynecology and Obstetrics surgical staging and survival rates in early endometrial carcinoma.

The medical records of patients with clinical Stage I endometrial adenocarcinoma who were treated at the Maimonides Medical Center between October 1979 and October 1987 were reviewed. There was sufficient surgical-pathologic information to allow a reclassification based on the new International Federation of Gynecology and Obstetrics (FIGO) surgical staging in 93 patients. These are the subjects of analysis. Twenty-one patients (23%) were found surgically to have more than Stage I disease. The 5-year survival rate for the whole group (N = 93) was 90%. However, it was significantly better for patients with surgical Stage I disease (98%) than for patients with surgical Stage III disease (60%) (P less than 0.001). There was no significant statistical difference in survival among patients with different substages within surgical Stage I (i.e., IA, 100%; IB, 100%; and IC, 88%), whereas the distribution of adjuvant therapy among these substages was not statistically different (P = 0.17). Thus, survival was not significantly affected by depth of myometrial invasion in patients who had negative peritoneal washing and no involvement of lymph nodes or the peritoneal cavity.

Adenocarcinoma↗
PubMed1995

Non-Hodgkin's lymphoma.

BACKGROUND: Significant advances in the understanding of non-Hodgkin's lymphoma (NHL) have occurred in the past two decades, resulting in changes in terminology and classification practices, which may affect the analysis of the Surveillance, Epidemiology, and End Results (SEER) data. METHODS: The incidence rates for each subgroup of NHL in the Working Formulation were reviewed from the National Cancer Institute's SEER data during three time periods: 1973-1977, 1978-1982, and 1983-1987. RESULTS: NHL has significantly increased by 50% from 1973 to 1988. The most frequently occurring NHL is diffuse large cell lymphoma, constituting nearly 30% of all lymphomas. Increased incidence rates for large cell immunoblastic and small noncleaved cell NHL observed during the 1980s are attributable largely to the acquired immunodeficiency syndrome epidemic. Exposure to environmental agents such as herbicides and hair coloring dyes have recently been identified as factors that increase the risk of NHL, but the overall contribution of these factors remains to be identified. The increase in extranodal lymphomas is in part a consequence of the application of modern immunophenotypic and genotypic methods, which lead to the reclassification of pseudolymphomas as monoclonal B-cell neoplasms. The apparent dramatic decline in the incidence of diffuse small cleaved NHL appears to be artifactual, as well, secondary to changes in classification of NHL. CONCLUSIONS: With the enhanced ability of pathologists to delineate new clinicopathologic entities by immunophenotypic and molecular biologic studies, future modifications to the collection of SEER data may be appropriate. Such an approach will address the limitations of the Working Formulation and lead to a more accurate data base for the evaluation of epidemiologic trends.

Adolescent↗
PubMed2000

Evaluation of the validity of the 1997 International Union Against Cancer TNM classification of major salivary gland carcinoma.

BACKGROUND: The TNM classification (International Union Against Cancer) of salivary gland carcinoma was revised in 1997. In this study, the authors have evaluated the validity of this new TNM classification and clinical staging in 1683 patients with parotid gland carcinoma. METHODS: Reclassification was conducted according to the new classification based on the clinical data of 1683 patients registered to the salivary gland division of the Japanese Joint Committee on TNM classification. The 5- and 10-year survival rates according to TNM classification were calculated for 1074 patients whose prognosis could be followed up. Finally, the distribution of the total patient population was analyzed using the new staging and the survival curves for each disease stage. RESULTS: The variance of the patients for T1 to T4 was appropriate using the new T classification. The 5- and 10-year survival rates corresponded well to the degree of progression of TNM. However, there were only nine patients with Stage III, and marked nonuniformity in the staging was observed. The separation of the survival curves for each stage was not clear, and no significant differences between the survival curves of Stages II and III and Stages III and IV were observed. When the authors classified T1N1M0, T2N1M0, T3N1N0, and T4N0M0, which have 5- and 10-year survival rates similar to Stage III, distribution of patients and separation of the survival curves in each stage improved markedly. CONCLUSIONS: The results of the current study confirm that the new TNM classification system is valid. However, a significant problem was observed with respect to the new clinical staging. The authors propose that T1N1M0, T2N1M0, T3N1M0, and T4N0M0 be classified as Stage III.

Disease-Free Survival↗
PubMed2000

Frequency and clinical impact of lymph node micrometastasis and tumor cell microinvolvement in patients with adenocarcinoma of the esophagogastric junction.

BACKGROUND: Tumor involvement of regional lymph nodes has a crucial impact on the prognosis of patients with adenocarcinoma of the esophagogastric junction (AEG). Although additional tumor cell deposits can be detected by sensitive methods (e.g., immunohistochemistry and polymerase chain reaction), their prognostic significance is uncertain. METHODS: Using immunohistochemistry for cytokeratins (AE1/AE3 antibody), the authors studied 3987 regional lymph nodes from 145 patients with completely resected adenocarcinoma of the esophagus (AEG I; n = 46 patients), cardia (AEG II; n = 79 patients), and subcardial region (AEG III; n = 20 patients). The newly detected cells were categorized with tumor cell microinvolvement (TCM) or with micrometastases (MM) based on tumor size and histology. RESULTS: Of the 75 pathologic lymph node negative (pN0) patients, 3 of 30 patients in the AEG I group (10%) and 8 of 45 patients in the AEG II and III groups (18%) had TCM (no significant difference). MM was found in 2 of 30 tumors in the AEG I group (7%) and in 11 of 45 tumors in the AEG II and III groups (24%), a significantly lower rate that that in the AEG I group (P < 0.05). Neither TCM nor MM showed a significant prognostic impact in AEG I tumors (P > 0.05). For the AEG II and III tumors, MM (new lymph node positive [pN+] cases) had a prognostic impact similar to metastases found by routine methods, with reclassification based on MM resulting in improvement in the pN0 group from 72.8 months to 82.6 months, but almost no change was seen in the pN+ group (49.9-49.2 months). TCM had no adverse impact on survival in any tumor type. CONCLUSIONS: These results highlight important differences between AEG I tumors and AEG II and III tumors and argue for different lymphadenectomy strategies for patients with these tumor types.

Adenocarcinoma↗
PubMed2000

Use of computer-assisted rescreening as an ancillary tool to subclassify AGUS cervical smears.

A substantial percentage of women with a diagnosis of atypical glandular cells of undetermined significance (AGUS) on cervical smears harbor a significant squamous or glandular, preneoplastic or neoplastic lesion on subsequent follow-up. Attempts to subclassify AGUS smears by conventional methods have had mixed results. To determine whether subclassification of AGUS cervical smears using computer-assisted rescreening based on the neural network would improve correlation with subsequent histologic follow-up, 91 cervical smears, conventionally diagnosed as AGUS without concomitant squamous lesions, were subjected to analysis by a computer-assisted automated screening system. Computer-generated images were evaluated by a cytotechnologist without the knowledge of the histologic outcomes. Prior to manual review, each case was classified as either within normal limits, no review required; or abnormal, review required. Based on the degree of abnormality, the latter category was further subclassified into either low probability or high probability of abnormality. The results of the computer-assisted reclassification were then compared with the histologic follow-up of all patients. Thirty-three cases (38.8%) had a significant lesion on histologic follow-up. The lesions included 4 CIN I, 7 CIN II/III, 12 endocervical adenocarcinomas (ACA), and 10 endometrial ACA. Based on computer-generated images, 65% of the smears that were triaged as high probability of abnormality, 11.5% that were triaged as low probability of abnormality, and 10.5% that were triaged as within normal limits had a significant lesion on subsequent follow-up. We conclude that computer-assisted rescreening aids in the triage of AGUS smears and that computer-assisted rescreening based on the neural network or other algorithms may be a useful ancillary tool for subclassifying AGUS cervical smears.

Adenocarcinoma↗
PubMed1978

The prediction of outcome from anhedonia and process-reactive scales.

Earlier researchers have suggested that the ability of process-reactive measures to predict future adjustment may result from their relationships to the anhedonia dimension. In the present study the abilities of process-reactive and anhedonia measures, independent of one another, to predict rehospitalization data were compared. After anhedonia scores had been partialed out, schizophrenics' process-reactive scores were correlated modestly with length of the patients' next hospitalization and reclassification as nonschizophrenic. No such significant correlations appeared between anhedonia and adjustment measures after process-reactive scores had been partialed out. Among nonschizophrenics, a sizeable correlation between anhedonia and the probability of later diagnosis of schizophrenia appeared, which suggests that anhedonia may be a useful prodromal marker for schizophrenia.

Adult↗