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[The development of metastases and their classification].

PURPOSE: The process of metastasis has been elucidated by thorough morphological studies on resection specimens and new findings in the field of molecular biology in recent years. The successful surgical removal of distant metastases lead to the necessity of a detailed and precise classification system of distant metastases. PATIENTS AND METHODS: The new molecular findings as well as data obtained from morphological studies and the results of a international field study on behalf of the UICC lead to the proposed system presented here as a new classification system for metastases. RESULTS: A general classification of distant metastases of any primary tumor should separate 5 different categories: M1 for non-regional lymph node metastases only, M2 for liver metastases only, M3 for lung metastases only, M4 for bone metastases only and M5 for metastases in 2 or more of these organs or others. In case of liver metastases of colorectal carcinoma, 2 different classifications were proposed; a clinical classification based on locoregional tumor status, number of liver metastases and involved lobes and a post-surgical classification depending on locoregional tumor status and size of metastases removed surgically and assessed by the pathologist. CONCLUSION: More detailed knowledge of the metastatic process and success in surgical treatment makes a detailed and exact classification system for distant metastases essential. This should be used as a fundamental base for future therapeutical and prognostic studies.

Classification↗

A new classification for malignant tumors involving the anterior skull base.

OBJECTIVES: To propose our clinical classification of malignant ethmoid tumors and to compare it with the last American Joint Committee on Cancer (AJCC)-Union Internationale Contre le Cancer (UICC) classification, published in 1997. DESIGN: Retrospective review. SETTING: Tertiary cancer facility. PATIENTS: We evaluated 123 consecutive patients undergoing craniofacial resection for malignant ethmoid tumors involving the anterior skull base. The mean follow-up was 60 months. Fifty-nine patients (48%) presented with recurrent disease after prior therapy. We classified them with a new classification system (Istituto Nazionale per lo Studio e la Cura dei Tumori) based on the most commonly accepted unfavorable prognostic factors (involvement of dura mater; intradural extension; involvement of the orbit and, in particular, of its apex; invasion of maxillary, frontal, and/or sphenoid sinuses; and invasion of the infratemporal fossa and skin. We also classified patients with the AJCC classification published in 1997. MAIN OUTCOME MEASURES: Disease-free status and overall survival rate. To study a possible association with tumor stage, the Cox regression model was adopted. RESULTS: According to our classification, patient distribution by tumor type was T2, n = 46; T3, n = 29; and T4, n = 48 (no T1 tumors were present in the series). For previously untreated patients, 5-year disease-free survival estimates were T2, 57%; T3, 50%; and T4, 13%. For relapses, corresponding figures were T2, 31%; T3, 23%; and T4, 1%. The prognostic difference among stages was statistically significant (P<.001). Similar results were obtained for overall survival. In contrast, patient distribution among different AJCC stages was less balanced, and we failed to detect a significant association with the clinical outcome using this classification. CONCLUSION: We propose the use of our staging system by all those specialists in the field willing to validate the classification and possibly apply it for clinical and investigational purposes.

Adult↗

Reliable computer-assisted classification of the EEG: EEG variants in index cases and their first degree relatives.

A method which optimizes on global properties of sample recordings is proposed for the definition of and the discrimination between electroencephalogram (EEG) classes. The sample was drawn from students at the University of Heidelberg from 1974 to 1978 and consists of 15 healthy index cases clinically ascertained as belonging to the low voltage EEG group. In addition, the three clinically defined groups: diffuse beta (18 index cases), borderline alpha (12 index cases) and monomorphous alpha (18 index cases) have been included in the study, as well as the first degree relatives of the index cases, thus providing a clinical classification into four groups. The proposed method provides an automatic and reliable classification algorithm using discriminant and cluster analysis. The relation between such an automatized classification and clinical classification schemes is investigated. In particular, the inheritance of the low voltage EEG, the question on sex differences and the question of a simple Mendelian mechanism had been examined. The method of random splittings had been applied for discriminant and cluster analysis. Our findings can be summarized as follows: (1) except for the monomorphous alpha EEG group, the clinical classification shows rather marginal separation (discriminating performance 60% to 75%), while a new and more reliable grouping scheme improves the discriminating performance up to 87% to 91%. The latter scheme leads to the concept of personal channel pattern (PCP) and was compared to the clinical classification scheme by means of contingency tables; (2) only a weak correlation between the clinically and PCP-based groups could be found (Cramér Index: 0.27). Accordingly, we continued to investigate the extent to which the proposed EEG classification scheme can nevertheless explain the genetic mechanisms apparently involved in the low voltage EEG. We thus considered the role of sex differences manifest in our proposed new grouping scheme; (3) males occurred more frequently in the new group 3 and females more frequently in the new group 1. In this regard, a much better correlation of the new groups between mothers and children than between fathers and children was observed; and (4) with help of our new PCP scheme, we have been able to reproduce a simple two gene Mendelian scheme to explain inheritance of the clinical low voltage EEG group. In this PCP-based scheme, the low voltage property does not occur when dominance of a certain gene (called gene A) is absent.

Adult↗

Classification of gastric carcinoma using the Goseki system provides prognostic information additional to TNM staging.

BACKGROUND: Due to the high variability of the epidemiology, genetics, morphology, and biologic behavior of gastric carcinoma, many classification systems are in use, e.g., the World Health Organization (WHO) classification; tumor differentiation; the criteria of Ming, Mulligan, and Laurén; and the recently introduced Goseki classification. In the authors' opinion, the TNM staging is the most valuable classification system, with a prognostic value for survival. METHODS: To assess the reproducibility and usefulness of these systems in clinical practice, material from 285 gastric carcinoma patients entered in the Dutch Gastric Cancer Trial was analyzed by a panel of 5 experienced gastrointestinal pathologists. The presence of eosinophilic and lymphocytic infiltrates was analyzed in addition to the TNM staging. RESULTS: Of the analyzed classification systems, only TNM stage, tumor differentiation, eosinophilic infiltrate, and the Goseki system contained information associated with the survival of patients with gastric carcinoma. The reproducibility was perfect for tumor differentiation (Kappa 1.00), nearly perfect for the WHO and Goseki classifications (Kappa 0.86 and 0.87, respectively), reasonably good for Laurén and lymphocytic infiltrate (Kappa 0.70), and reasonably good for eosinophilic infiltrate (Kappa 0.42). CONCLUSIONS: Of all these systems, the Goseki classification was the only system with prognostic value that is additional to TNM staging.

Adenocarcinoma↗

The international classification of childhood cancer.

The International Classification of Childhood Cancer (ICCC) updates the widely used Birch and Marsden classification scheme. ICCC is based on the second edition of the International Classification of Diseases for Oncology (ICD-O-2). The purpose of the new classification is to accommodate important changes in recognition of different types of neoplasms, while preserving continuity with the original classification. The grouping of neoplasms into 12 main diagnostic groups is maintained. The major changes are: (1) intracranial and intraspinal germ-cell tumours now constitute a separate subgroup within germ-cell tumours; (2) histiocytosis X (Langerhans-cell histiocytosis) is excluded from ICCC; (3) Kaposi's sarcoma is a separate subgroup within soft-tissue sarcomas; (4) skin carcinoma is a separate subgroup within epithelial neoplasms; (5) "other specified" and "unspecified" neoplasms are now usually separate sub-categories within the main diagnostic groups. Draft copies of the ICCC were distributed to some 200 professionals with interest and expertise in the field and their comments are considered in this final version. This classification will be used for presentation of data in the second volume of the IARC Scientific Publication "International Incidence of Childhood Cancer." A computer programme for automated classification of childhood tumours coded according to ICD-O-1 or ICD-O-2 is now available from IARC.

Bone Neoplasms↗

Association between mammographic parenchymal pattern classification and incidence of breast cancer.

Wolfe has suggested that the mammographic parenchymal patterns can be used to identify a group with high incidence of breast cancer. To evaluate this claim, mammograms of women with breast cancer that was detected at the University of Michigan Breast Cancer Detection Demonstration Project have been classified and compared with a randomly selected control group from the same project. The basic mammographic classifications as defined by Wolfe were used with further refinements made in the DY and QDY groups. The mammographic classifications have been grouped according to the degree of density and age. For all ages combined, our dense classifications (DY1, DY2, DYC-, QDY2) show a higher incident rate, 22/1000,than the lucent classification (N1, P1, and QDY1),9/1000,(P less than .01), although not to the degree suggested by Wolfe. This difference is statistically significant (P less than .01); the higher risk is markedly increased for women under 50 years of age (P less than .005). After age 50 the higher risk associated with the dense breast seems to disappear (P less than .13). However, this might be a consequence of women who were in a dense classification at an earlier age who subsequently changed to a lucent classification later in life. Because the percentage of lucent breasts increases with age there is a higher absolute number of cancers (55%) in this group of women past 50; these women cannot be neglected in screening. Our results suggest the following guidelines for clinical evaluation: (1) Careful mammographic and clinical follow-up for any woman with a dense breast at any age. (2) Careful mammographic and clinical follow-up past 50 regardless of breast classification. (3) Women with lucent breasts under age 50 represent a low risk category and may not require as frequent a follow-up as the other mammographic types.

Adult↗

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↗

Phenotypic classification of human CD8+ T cells reflecting their function: inverse correlation between quantitative expression of CD27 and cytotoxic effector function.

Phenotypic classification of human CD8(+) T cells using three cell surface markers, CD27, CD28 and CD45RA, was recently suggested to be useful for identification of naive, memory and effector CD8(+) T cells. However, it still remains unclear whether such classification precisely reflects functional classification of CD8(+) T cells. To clarify this, we characterized each CD27CD28CD45RA subset of total and human cytomegalovirus (HCMV)-specific CD8(+) T cells by analyzing the expression of perforin and two chemokine receptors, CCR5 and CCR7, as well as their function. An inverse correlation between perforin and CD27 expression was found in all four CD28CD45RA subsets. Therefore, to achieve a phenotypic classification of CD8(+) T cells that more precisely reflects their function, the CD27(+) subset was divided into CD27(low) and CD27(high) subsets based on the expression level of CD27. Functional and flow cytometric analyses of CD27CD28CD45RA subsets showed that this phenotypic classification reflects functional classification of CD8(+) T cells. HCMV-specific CD8(+) T cells from healthy HCMV-seropositive individuals were predominantly found in effector and memory/effector subsets, indicating that HCMV-specific effector CD8(+) T cells are actively induced by HCMV replication in healthy HCMV carriers. Phenotypic analyses of CD8(+) T cells using this classification will enable the characterization of antigen-specific CD8(+) T cells.

CD28 Antigens↗

Radiographic classification of osteogenesis during bone distraction.

Successful limb lengthening requires serial radiological evaluation of the progression of healing of the regenerate bone. However, there is no radiographic classification system that shows how the regenerate should progress during treatment in adults. The study aimed to address this need.A series of radiographs were studied from 92 patients (125 segments) who had undergone bone lengthening. A radiographic classification of osteogenesis was developed based on callus shape and radiographic features that occur between osteotomy and fixator removal. This classification system used both shape and type of feature to condense and record the radiographic information, but type of feature alone was sufficient to predict outcome. The concurrence and reproducibility of the classification system was tested by inter- and intra-observer studies. The degree of consistent repetition and agreement between observers suggests that the classification system is reliable, reproducible, and therefore should be robust in use. This classification system provides an insight into osteogenesis; it allows the progress of the bone healing to be assessed against a successful pattern of healing. Hence, potential problems can be predicted and clinical changes made to improve outcome. The classification can be simplified to make it more appropriate for clinical use.

Adolescent↗

Protein classification artificial neural system.

A neural network classification method is developed as an alternative approach to the large database search/organization problem. The system, termed Protein Classification Artificial Neural System (ProCANS), has been implemented on a Cray supercomputer for rapid superfamily classification of unknown proteins based on the information content of the neural interconnections. The system employs an n-gram hashing function that is similar to the k-tuple method for sequence encoding. A collection of modular back-propagation networks is used to store the large amount of sequence patterns. The system has been trained and tested with the first 2,148 of the 8,309 entries of the annotated Protein Identification Resource protein sequence database (release 29). The entries included the electron transfer proteins and the six enzyme groups (oxidoreductases, transferases, hydrolases, lyases, isomerases, and ligases), with a total of 620 superfamilies. After a total training time of seven Cray central processing unit (CPU) hours, the system has reached a predictive accuracy of 90%. The classification is fast (i.e., 0.1 Cray CPU second per sequence), as it only involves a forward-feeding through the networks. The classification time on a full-scale system embedded with all known superfamilies is estimated to be within 1 CPU second. Although the training time will grow linearly with the number of entries, the classification time is expected to remain low even if there is a 10-100-fold increase of sequence entries. The neural database, which consists of a set of weight matrices of the networks, together with the ProCANS software, can be ported to other computers and made available to the genome community. The rapid and accurate superfamily classification would be valuable to the organization of protein sequence databases and to the gene recognition in large sequencing projects.

Computers, Mainframe↗

Valuing of identity, distribution of attention, and perceptual salience in free and rule-governed classifications.

This experiment investigated classifications of multidimensional objects to test whether (1) the valuing of identity as a classification criterion occurs early in development, (2) the distribution of attention to multiple relations increases with development, and (3) the role of separate, component relations in solving multidimensional classification problems would be manifested through measures of perceptual salience. A salience preassessment followed by free and rule-governed classification tasks were given to 4-, 7-, and 18-year-olds. Total identity, partial identity, overall similar, or overall different choices were available for classification. Results associated with both free and rule-governed classifications indicated that identity serves as a highly valued classification criterion beginning as early as 4 years of age. Results associated with salience indicated that children as young as 4 years perceive and process relations separately and that 4-year-olds show greater differential attention than older children and adults.

Adolescent↗

Review of international criteria and mixture rules for health hazard classification.

The presentation of consistent hazard information in the face of conflicting inter- and intranational regulations and standards is a formidable task. The principal challenge arises from the varying definitions of what is and is not a hazardous chemical and the differing rules that regulate the disclosure of components on material safety data sheets (MSDS) and labels. Some of the effects on hazard communication of nine health hazard classification systems of the United States, Canada, and the European Union are analyzed. The additional complication of differing rules that govern the hazard classification of mixtures is also discussed. The combination of inconsistent hazard classification of individual chemicals and dissimilar mixture rules can result in different conclusions about the hazard classification of commercial products. Faced with this situation, hazard communicators must focus on developing clear statements of the health effects that may arise from overexposure to a chemical, which is the essential purpose of developing MSDS and labels. These statements may be distinct from the terminology derived from the various classification systems. All national MSDS systems make provisions for including statements of hazard and also for providing the toxicology information that is the basis for translation into the locally governing classification terminology. Requirements for labels are often more restrictive, and the complete resolution of conflicting communication must await international harmonization of hazard classification systems including mixture rules.

Air Pollutants, Occupational↗

[Problems of clinical evaluation of hemodynamics at rest and during exercise in chronic heart disease. Value of cardiac catheterization and problems of clinical classification].

BACKGROUND: NYHA classification is mostly used for graduation of clinical limitation due to cardiac failure. Right heart catheterization is not generally used to evaluate hemodynamics and to define the effects of drugs in patients with chronic cardiac failure. Clinical data and results from echocardiography, stress tests or nuclear cardiology seem to be sufficient. Our aim was to demonstrate subjectivity of a classification system (NYHA) comparing the graduation done by physicians and by patients and to represent the difficulty to prognosticate hemodynamic data of patients with heart failure. PATIENTS AND METHODS: Limitation of 53 patients with heart diseases was classified by physicians and patients using NYHA classification. Pulmonary capillary wedge pressure (PCWP), stroke volume (SV) and cardiac output were predicted by physicians; they were allowed to utilize all examination data they could get. Predicted hemodynamic data were compared with the results of measurement at rest and during exercise. RESULTS: Patients classified themselves significantly worse than physicians did: 2.68 +/- 0.64 vs. 2.23 +/- 0.74 (p = 0.0012). Similarity in NYHA classification was found in 29/53 cases. Correlation of predicted and measured hemodynamic data was low: PCWP (at rest) r = 0.346; PCWP (during exercise) r = 0.232; SV (at rest) r = 0.476; SV (during exercise) r = 0.445; HMV (at rest) r = 0.412; HMV (during exercise) r = 0.538. CONCLUSION: Clinical classification systems like NYHA are subjective, classification by physicians differs significantly from classification by patients. Prediction of hemodynamics is not possible despite all examination data had been available. Right heart catheterization is necessary to define hemodynamics at rest and during exercise.

Cardiac Catheterization↗

Outcome of patients with non-Hodgkin's lymphoma of the stomach after gastrectomy: clinicopathologic study and reclassification according to the revised European-American lymphoma classification.

BACKGROUND: The best treatment for patients with non-Hodgkin's lymphoma (NHL) of the stomach is still uncertain. The revised European-American lymphoma (REAL) classification has helped to define new, potentially more appropriate classification schemes for gastric lymphomas. METHODS: Fifty-one resected gastric lymphomas were reclassified according to the REAL classification, and the efficacy of multimodal treatment was examined retrospectively. The principal treatment plan consisted of: (1) surgical resection of the stomach with lymph node dissection, followed by (2) systemic chemotherapy, mainly using the cyclophosphamide/doxorubicin/vincristine/prednisone (CHOP) regimen. RESULTS: According to the Ann Arbor classification, 27 patients had stage IE, 19 had stage IIE, and 5 had stage IV NHL. Using the REAL classification, we diagnosed diffuse large B-cell lymphoma (DLBL) in 23 patients, marginal zone B-cell (low-grade mucosa-associated lymphoid tissue [MALT]-type) lymphoma in 22, follicle center lymphoma in 4, mantle cell lymphoma in 1, and peripheral T-cell lymphoma in 1 patient. Nine of the 51 patients relapsed, and 8 patients with DLBL died of cancer. Survival rates at 5 years after surgery were 96.0% for stage IE, 83.3% for stage IIE, and 87.0% for all patients. Univariate analysis indicated that the tumor histology (according to the REAL classification), depth of invasion, degree of nodal involvement, Ann Arbor staging, and chemotherapy had an impact on patient outcome (P = 0.0018; P = 0.0002; P = 0.0308; P = 0.0016, and P = 0.0118, respectively). CONCLUSIONS: These data reveal that gastric NHL, especially of the low-grade MALT-type, often remains localized and has a good prognosis after surgery. The REAL classification was useful for classifying new categories of NHL, including the MALT-type, in the clinical setting, and for determining the optimal treatment modality for gastric NHL.

Female↗

[The new "Vienna Classification" for epithelial neoplasia of the gastrointestinal tract. Pros or cons?].

A number of seminars have shown considerable differences between Japanese and Western pathologists in the the diagnostic differentiation of regenerative changes, dysplasia, and well differentiated adenocarcinoma in gastroenterological biopsy material. Lesions which most Western pathologists identify as "dysplasia" are often considered adenocarcinomas in Japan. A comparison of the biopsy-based diagnoses with those established in resected mucosa, however, reveals appreciable diagnostic inexperience on the part of Western pathologists, with significant discrepancies between their diagnoses based on biopsies and those based on resected material. Against this background, a new classification of epithelial neoplasias of the gastrointestinal tract was drafted on the occasion of the World Congress of Gastroenterology in Vienna in 1998. By collapsing the diagnoses "high-grade adenoma/dysplasia, noninvasive carcinoma (carcinoma in situ), and suspected invasive carcinoma" into a single category ("noninvasive high-grade neoplasia," category 4), this scheme should largely eliminate the diagnostic discrepancies between Western and Japanese pathologists. As with every classification, the Vienna classification has its advantages and disadvantages; these are discussed here. The most important advantage of the Vienna classification is that the various categories are associated with different recommendations for further diagnostic and therapeutic measures. This applies particularly to category 4, with the recommendation for only local treatment initially (endoscopic mucosal resection or surgical excision). Since the introduction of the Vienna classification the new WHO classification of neoplasias of the gastrointestinal tract has recently been published, in which the term dysplasia has been replaced by "intraepithelial neoplasia." This means that the Vienna classification needs to be modified accordingly.

Carcinoma, Squamous Cell↗

An assessment of the usefulness of screen-film speed classifications.

Speed classifications of screen-film combinations are frequently quoted in the day-to-day functioning of X-ray departments. These values are utilised for a variety of functions by X-ray personnel. This study aimed to compare a range of commonly used screen-film combinations in order to establish the level of agreement between stated speed classifications and actual speed of systems. Relationships between system speed class and image quality were also investigated. Six commonly used screen-film systems were studied; three had a speed classification of 200 while the remaining systems had a classification of 400. Characteristic curves for each system were produced, from which relative speeds were calculated at four beam energies. Psychophysical tools and visual grading analyses were used to assess image quality. The sensitometric results demonstrated that at all energies the speed class quoted did not predict the actual relative speeds of the film-screen systems. The image quality study demonstrated disagreement with conventional assumptions regarding speed classifications with mean values for 400 speed systems being higher or at least equal to the 200-system scores. There is no evidence from this study to support the ongoing use of current screen-film classifications. Personnel within all X-ray departments should carry out rigorous speed measurements and image quality assessments of all systems within their department before nominal classifications are used.

Radiography↗

AO or Schatzker? How reliable is classification of tibial plateau fractures?

INTRODUCTION: We compare the intra- and interobserver reproducibility of classifications of tibial plateau fractures most commonly used in our clinical practice. These were the AO and Schatzker classifications. PATIENTS AND METHODS: Agreement was measured using kappa coefficients on the data obtained from three observers reviewing 30 fractures and these values were interpreted according to Landis and Koch. RESULTS: It was found that both classifications were substantially reliable with regards to intraobserver reliability but that the Schatzker system was only fairly reliable and the AO classification moderately reliable with regards to interobserver reliability. Breaking down the AO classification, with regards to intraobserver reliability, the AO group was substantially reliable and the type excellently reliable. For interobserver reliability, the AO group was moderately reliable while the AO type was substantially reliable. CONCLUSION: For tibial plateau fractures seen on plain x-ray, the AO classification is more reliable between observers than the Schatzker classification.

Humans↗

Perception of Garden's classification for femoral neck fractures: an international survey of 298 orthopaedic trauma surgeons.

The Garden classification is the most popular femoral neck fracture classification system. We surveyed orthopaedic surgeons about their preferences for femoral neck fracture classification systems and their belief about their ability to discriminate between the four different Garden fracture types. A questionnaire was developed to examine surgeons' training and experience and their preferences for classification of femoral neck fractures by consulting five orthopaedic surgeons in Canada and the United States, and the previous literature. The Garden classification was the preferred femoral neck fracture classification for 72% of all the surveyed surgeons (n=298). Only 39% of all the surveyed surgeons believed they were able to distinguish all four Garden fracture types. However, 96% of the surgeons felt they could differentiate between undisplaced (Garden I/II) and displaced (Garden III/IV) fractures. High variability in the surgeons' perceptions of the Garden classification system provides a rationale for discontinuing the use of this system in daily practice.

Adult↗